Peripheral Capillaries Research Articles

Feto-placental circulatory competence

Doppler assessment of the pulsatility index (PI) of umbilical artery blood velocities offers promise as a simple, non-invasive method for early diagnosis of placental failure. The present report identifies the hemodynamic factors determining this PI, based on current knowledge of feto-placental physiology. It is postulated that the umbilical artery PI is mainly determined by the ratio of capillary to arterial resistances in the fetal placental circulation. However, the biological PI variations on a minute by minute basis are caused by short-term variations in blood pressure pulsatility. The ratio of resistances declines markedly with advancing pregnancy, indicating that the site of predominant resistance determining the volume of placental blood flow gradually migrates from the peripheral capillary to the arterial compartment. After 28 wk of gestation, umbilical artery PI values decrease below 1, reflecting the normal reserve capacity of the functional capillary bed of the placenta. PI values above 1 in the last trimester reflect a critical enhancement of placental capillary resistance, which must impede blood flow to functional chorionic villi. It is concluded that this Doppler technique may provide a simple method for clinical assessment of placental circulatory competence.

Accumulation of laminin and type IV collagen in the kidney in congenital nephrosis

The aim of this study was to evaluate qualitatively the occurrence of the basement membrane proteins laminin and type IV collagen in the kidneys of ten infants with congenital nephrotic syndrome of the Finnish type (CNF) aged from 3 to 23 months and to compare the results with those for age-matched controls. A slow accumulation of basement membrane (BM) material occurred in the glomerular mesangium, the peripheral capillaries, around atrophied tubules, and the renal vessels in the course of the disease. The staining pattern of accumulated material depended on the duration of the disease and subsequent renal parenchymal damage. Young CNF patients with slight morphological changes in the kidney had only focal and minimal increases in the amounts of mesangial matrix, but as the disease advanced, so the BMs of the glomerular capillaries, renal arteries, and atrophied tubules also became involved and were thicker than normal. The staining reaction was in all patients similar with antibodies against the fragment P1 of laminin and the 7-S domain of type IV collagen. The accumulation of BM material in CNF kidneys is regarded as a secondary phenomenon induced by an unknown pathogenetic defect in the metabolism of some BM component.

Effects of transfusion-induced polycythemia on O2 transport during exercise in the dog.

An increased hematocrit could enhance peripheral O2 transport during exercise by improving arterial O2 content. Conversely, it could reduce maximal delivery of O2 by limiting cardiac output during exercise or by limiting the distribution of blood flow to peripheral capillaries with high O2 extractions. We studied O2 transport at rest and during graded treadmill exercise in splenectomized tracheostomized dogs at normal hematocrit (38 +/- 3%), and 48 h after transfusion of type-matched donor cells. This procedure increased hematocrit (60 +/- 3%) but also increased blood volume (P less than 0.05). Following transfusion, resting cardiac output (QT) and heart rate were not different. During exercise, QT was significantly lower at each level of O2 consumption (VO2) at high hematocrit (P less than 0.01). A reduction in QT was also seen during polycythemic exercise with hypoxemia produced by breathing 12 or 10% O2 in N2. Despite the reduction in QT, mixed venous PO2 was not lower at high hematocrit, and the increase in base deficit with VO2 was not different from control measurements. O2 delivery (QT X arterial content) was similar at each level of VO2 at both levels of hematocrit, during both normoxic and hypoxic studies. Both systemic and pulmonary arterial pressures were increased at rest after transfusion (P less than 0.05). However, pulmonary and systemic pressures were not higher than control during exercise at high hematocrit. We conclude that a hematocrit of 60% with increased blood volume is not associated with a cardiac limitation of O2 delivery, nor does it interfere with peripheral O2 extraction during exercise in the dog.

The ultrastructural localization of two basement membrane components: entactin and laminin in rat tissues.

The localization of two noncollagenous components of basement membranes, laminin and entactin, was determined in rat kidney, muscle, and small intestine using electron immunohistochemistry. In the renal glomerulus anti-laminin antibodies reacted with the basement membrane of peripheral capillary loops and with mesangial matrix. In the peripheral capillary loop laminin was preferentially distributed in both laminae rarae. This was in contrast to anti-entactin that localized in peripheral capillary loops but not in mesangial matrix. Even in the peripheral capillary loops it had a different distribution than laminin. Entactin was found predominantly in the lamina rara interna. In renal tubular basement membranes both antibodies localized throughout the full thickness of the basement membranes, with laminin having a preferential distribution in the lamina rara, whereas entactin was more evenly distributed. In the basement membrane of the duodenal mucosa entactin localized in the lamina densa, whereas laminin was present in both laminae. In skeletal muscle both antibodies had similar localization in all basement membranes. These results demonstrate that entactin is an intrinsic component of basement membranes. They also demonstrate that basement membranes from different tissues have subtle variations in content and/or assembly of the different components. It is likely that these variations may be reflected in different functional properties.

Idiopathic intrauterine growth retardation: Histomorphometry of the human placenta

The morphological changes in the functional structure of the placenta in cases of idiopathic intrauterine growth retardation (IUGR) have been investigated with quantitative analyses. It has shown that the placentae of the small-for-gestational-age (SGA) infants were 45 per cent smaller than the controls, due to an almost equal reduction in parenchymal (48 per cent) and non-parenchymal (42 per cent) tissues. Consequently, in relative values the placentae of the SGA infants were shown to be otherwise very similar to the controls. In contrast, in absolute values, the placentae of the growth-retarded infants were shown to differ from the controls by having significantly less surface area of exchange between mother and fetus, mainly in terms of peripheral capillary (3.85 vs 7.21 m2; P less than 0.02) and villous (4.31 vs 8.74 m2; P less than 0.005) surface areas, and intervillous space volume (53.71 vs 103.26 cm3; P less than 0.001). The total number of cells (53 418 x 10(6) vs 104 820 x 10(6); P less than 0.005) was also shown to be markedly decreased in the placentae of the SGA infants, compared with the controls, and the placental membrane showed a 51 per cent decrease in trophoblast mass or cellular content. On a functional basis, these findings suggest that, in these cases of idiopathic IUGR, the placental morphological changes are bound to produce placental insufficiency and fetal growth retardation.

Morphometric analysis of basal laminae in rats with long-term streptozotocin diabetes L. II. Retinal capillaries

Twelve months after onset of streptozotocin-induced diabetes in rats, the basal lamina width of peripheral retinal capillaries, as measured with two different morphometric methods, is increased only in the basal lamina regions adjacent to perivascular glial cells. In the region between endothelial cells and pericytes no increase of thickness was observed. These facts support the suggestion of a predominantly glial (neuroectodermal) contribution to basal lamina thickening of retinal capillaries in diabetes mellitus. No correlation exists between the degree of basal lamina thickening at the different anatomic sites. Furthermore, no clear-cut correlation was found between basal lamina thickening and severity of the metabolic disease.

Peripheral Circumferential Retinal Scatter Photocoagulation for Treatment of Proliferative Sickle Retinopathy

Twenty-nine patients (40 eyes) with proliferative sickle retinopathy (PSR) were treated with circumferential argon laser scatter photocoagulation to zones of peripheral retinal capillary nonperfusion. Each eye was examined in a prospective fashion, with a mean follow-up of 1.4 years. Following scatter treatment, 26% of pre-existent sea fans regressed completely, 57% regressed partially, 17% remained stable, and none showed progression. In only one eye did de novo neovascularization develop. The results compare favorably with the natural history of PSR (Condon et al, 1980), in which de novo lesions occurred in 58%, and the visual acuity was decreased to less than 20/200 in 12% of affected eyes. Severe iatrogenic complications reported following direct focal treatment of sea fans, such as vitreous hemorrhage, progressive traction retinal detachment, retinal breaks, and choroidal-retinalvitreal neovascularization were virtually elminated.

A superb transport system — The circulation

This paper discusses certain aspects of circulatory physiology, including foetal circulation and the role of the thorax, and gives parameters for total blood volume, cardiac output, stroke volume and the distribution of blood between the pulmonary and peripheral circulation within the horse. The reader is taken on a journey around the circulatory system, beginning in the left atrium, into which richly oxygenated blood runs from the pulmonary veins. From here the blood is squeezed via the mitral valve into the left ventricular pump, where it is forced under high pressure through the peripheral circulation, the arterioles and capillaries, to collect, deoxygenated and under much lower pressure, into the venules and veins. The pumping action of the muscles and the negative intrathoracic pressure help to draw the blood back up to the right atrium, itself exerting a suction effect on the great veins. The blood is then expelled from the right ventricle into the low resistance, high capacitance pulmonary circuit, where it picks up oxygen, releases carbon dioxide and returns to the left atrium.

Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus.

To further characterize the IgA deposits found in glomeruli of patients with IgA nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus, renal biopsies from patients with these disorders were stained by immunofluorescence with monoclonal anti-IgA subclass reagents, anti-light chain reagents and anti-J chain. The mesangium and peripheral capillary were brightly stained for IgA1 and were negative for IgA2. IgA1 and, to a lesser extent, IgA2 were contained in tubular casts. Both kappa and lambda light chains were found in all deposits. The intensity of J chain staining correlated with the intensity of IgM and not IgA staining. Biopsies brightly stained for IgA but negative for IgM were negative for J chain. These results indicate that glomerular IgA deposits in these disorders consist predominantly of monomers of IgA1.

Fibronectin localization in the rat glomerulus.

Fibronectin (FN) has been localized in the rat glomerulus using indirect immunolabeling. It was demonstrated in frozen sections by immunofluorescence, in sections of fixed kidneys by both peroxidase and ferritin-labeled antibodies, and in isolated glomerular basement membranes (GBM) with ferritin-labeled antibodies. Complementary and convergent results were obtained with these approaches. FN was most abundant in the mesangial matrix where it was especially concentrated at the interface between the endothelial and mesangial cells. In the peripheral capillary loop, FN was also detected in the laminae rarae (interna and externa) of the GBM--i.e., between the endothelial and epithelial cells, respectively, and the GBM. These findings indicate that FN is an important constituent of the glomerulus, and they are compatible with the assumption that, in the glomerulus, as in cultured cells, FN is involved in cell-to-cell (mesangial-mesangial, mesangial-endothelial) and cell-to-substrate (mesangial cell-mesangial matrix, epithelium-GBM, endothelium-GBM) attachment.

The angiographic pattern of the peripheral retinal vasculature.

Various diseases of the peripheral retinal vasculature, such as sickle cell retinopathy and Eales' disease, demonstrate vascular abnormalities. For comparative purposes, we documented angiographically the peripheral retinal vasculature in young, healthy subjects. Our findings showed the density of the capillary bed to be highest in the posterior pole and least concentrated toward the periphery. Peripheral capillaries are considerably larger than those found posteriorly and have fewer bifurcations. Our technique also detected the periarterial capillary-free zone and the zone without capillaries adjacent to the ora serrata. These aspects were consistent with findings of other investigators using in vitro techniques. By creating a standard of normalcy in vivo, the angiographic technique allows vascular abnormalities evident in diseases of the peripheral retinal vasculature to be more precisely defined and compared.

Capillary distribution and metabolic histochemistry of the lateral propulsive musculature of pelagic teleost fish

Metabolic and vascular adaptation of teleost lateral propulsive musculature to an active mode of life was investigated in four pelagic teleosts (mackerel, yellowtail scad, pilchard and Australian salmon). Histochemical profiles and capillarisation data of the red and white muscle were compared to those of less active demersal species. Pelagic white muscle stained positively for the aerobic enzymes succinate dehydrogenase and NADH diaphorase, and had both subsarcolemmal and intermyofibrillar mitochondria which corresponded to the loci of the histochemical stain. Subsarcolemmal mitochondria tended to be localised close to capillaries. In contrast, white muscle from demersal species was unstained for the same enzymes and was devoid of mitochondria. Red muscle of all species had abundant mitochondria and stained intensely for aerobic enzymes. Capillarisation was quantified by determining the percentage of fibres surrounded by a given number of peripheral capillaries, mean fibre diameter, mean number of peripheral capillaries, capillary: fibre ratio and sharing factor where appropriate. Red muscle of mackerel, Australian salmon, pilchard and scad are better vascularised than red muscle of the flathead having 153, 200, 242, 291 and 309 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. White muscle of mackerel, pilchard and scad are better vascularised than white muscle of the Australian salmon and flathead having 2040, 3367, 4992, 9893 and 10,469 microns 2 of cross-sectional fibre area per peripheral capillary, respectively. Red muscle of Australian salmon had distinct regional variation. Deep red muscle was found to be more highly vascularised (4.2 peripheral capillaries per muscle fibre) than lateral red muscle (1.9 peripheral capillaries per muscle fibre). Red muscle of the other species was less heterogeneous. White muscle capillarisation was slightly variable in all species. It is concluded that the white muscle of the pelagic species studied is functionally and structurally adapted for sustained aerobic activity with relatively abundant mitochondria being preferentially situated close to the source of gas and metabolite exchange.

Retinal vessls of canine eyes at different ages—A qualitative and quantitative study

Diameter and number of cells per unit length of vessel wall and endothelial cell frequency were determined in capillaries of trypsin-digested Foxhound retinas from different age groups. Capillary diameters increased and number of cells per unit length of capillary wall decreased with age and distance from the optic disc. Endothelial cell frequency was constant at approximately 79% of the total cells in capillary walls in all areas measured. Peripheral cystoid degeneration and peripheral annular and focal degeneration were found in aged dog retinas. Sclerosis of retinal arterioles was observed ophthalmoscopically, histologically, and in trypsin-digested retinas from aged dogs. The significance of this change in relation to the peripheral retinal degeneration is undetermined. It is proposed that thickening of basement membranes observed in peripheral capillaries of retinas causes chronic, low-level hypoxia leading to peripheral retinal degeneration in aged retinas.

Talc Emboli and Retinal Neovascularization in a Drug Abuser

A 38-year-old male drug abuser had multiple emboli in the retinal circulation of the posterior pole of both eyes. He showed widespread peripheral retinal capillary nonperfusion and neovascular proliferation at the junction of perfused and nonperfused retina. The emboli were considered to be talc particles from the intravenous administration of suspensions of oral medications. The presumed mechanism of development of neovascularization in this case was the filtering out of the particles by the retinal vasculature with vaso-occlusion, ischemia and subsequent retinal neovascularization.

Diabetes and Glomerulopathies

To the Editor.— The article entitled, Acute Glomerulonephritis Complicating Diabetic Nephropathy, by Drs Olivero and Suki ( Arch Intern Med 137:732-734, 1977) reminded me of three nearly consecutive biopsies in diabetics that proved puzzling to Dr Paul Kimmelstiel and myself when we encountered them in 1968 (see Table). Report of Cases.—Case 1.— Patient 1 had a ten-day history of nausea and vomiting, and a three-day history of edema and dyspnea. Dr Kimmelstiel's biopsy interpretation was: The differential diagnosis lies between a diffuse diabetic glomerulosclerosis and lobular glomerulonephritis. In favor of the latter is the marked degree of cellularity, including polymorphonuclear leukocytes; against it are a clearly delineated basement membrane of peripheral capillaries. The possibility of a glomerulonephritis superimposed upon diabetic glomerulosclerosis must be considered. Case 2.— Patient 2 delivered a normal infant complicated by toxemia of pregnancy. Three months later, a biopsy was performed because of nausea, vomiting, persistent

Diabetic capillaropathy

Diabetic capillaropathy is defined and reviewed. A number of physiological and pathological variables, such as aging, venous stasis, and environment, may affect the thickness of the capillary basal lamina. Since these effects have not been adequately measured, it is impossible to know precisely what increment diabetes mellitus adds to the basal lamina. Because of these variables and technical difficulties, the detection of early diabetes is impossible at this time. However, the ultrastructure of the peripheral capillaries in the late stages of diabetes provides a means of detecting the presence of widespread capillaropathy when clinical evidence is difficult to obtain or uncertain.

Electron microscopic study on the response of the normal canine brain to boron-neutron capture therapy.

The response of normal cerebral tissue of dogs to boron-neutron capture therapy by the currently available improved method was studied by electron microscopy. Peripheral blood capillaries of the neutron-irradiated area in the left cerebral hemisphere were compared with their counterparts in the shielded and non-irradiated right hemisphere. No ultrastructural changes, as those noted in classical method of boron-neutron irradiation by the improved technique of boron-neutron capture therapy. There was no swelling of endothelial cells, disappearance of cristae of mitochondria, increased pinocytosis, disappearance of ribosomes, enlargement of Golgi apparatus, or increased appearance of endoplasmic reticulum. Basement membrane was not disrupted and was uniform. Pericytes, synaptosomes, and other glial elements remained intact. In contrast to the old clinical trials up to 1961, the renewed boron-neutron capture therapy is regarded not to cause serious damage to the central nervous system.

Pathophysiology of staphylococcal enterotoxin, Type B, (SEB) toxemia after intravenous administration to monkeys

Type B staphylococcal enterotoxin (SEB) is a single-chain protein of known amino acid composition and sequence. In highly purified form, SEB given orally to rhesus monkeys caused non-lethal illness characteristic of staphylococcal food poisoning. In contrast, after its intravenous administration, SEB produced fever and leukopenia followed by leukocytosis, and shock. Shock developed through pathophysiologic mechanisms generally similar to those which accompanied bacterial lipopolysaccharide endotoxemia, i.e. a pooling of blood in peripheral capillaries. After its intravenous administration, purified SEB disappeared rapidly from plasma. A major portion of the toxin was cleared by the kidneys, accumulating within proximal tubular cells. SEB toxemia could be prevented by prior administration of specific antitoxin, or treated after its onset by antitoxin. The purified SEB also produced in vitro effects on single cells which included: (a) induction of mitosis in lymphocytes, (b) generation of a chemotactic factor for neutrophiles, (c) inhibition of macrophage migration, (d) cytotoxicity in selected tissue cultures, and (e) induction of mitochondrial swelling in hepatocytes. Each of these effects of SEB on single cells was blocked by the inclusion of antitoxin in the reaction media. Although the primary site of SEB toxicity remains unknown, vascular endothelial cells may be a primary target.

Introduction: O2 Transport

The PO2 of blood in peripheral tissue capillaries depends upon: (1) the rate of blood flow; (2) the oxygen content of arterial blood; (3) the rate of oxygen consumption by the tissues; and (4) the oxygen affinity of the blood. The parameters are regulated and integrated in mammals at rest so that the PO2 in mixed venous blood is maintained at 35 ± 5 mm Hg over wide ranges of oxygen consumption, arterial blood O2 content and affinity, and blood flow. Furthermore, when a change in any one of these parameters is induced, the others respond in directions which tend to maintain mixed venous PO2.

Electron Microscopic Observations on Paravascular Retinal Rarefaction and Acellular Capillaries in a Senile Human Eye

In a senile human eye, formation of a large perivascular space around peripheral retinal capillaries was observed, followed by densification, rarefaction and finally total necrosis of the paravascular