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Myocyte hypertrophy and capillarization in spontaneously hypertensive stroke-prone rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) are liable to suffer a stroke between 25 and 40 weeks of age. Left ventricular capillarity was studied in 40-week-old SHRSP to clarify the effects of hypertrophic changes in cardiomyocytes on oxygen transport capacity within the tissue. The innermost region of the left ventricular subendocardium at the level of the maximum diameter of the heart was investigated. Methods for sectioning and differential staining of arteriolar, intermediate and venular capillaries, and measurements for determining capillarity parameters were as previously described. Total capillary density decreased, while capillary domain areas increased along the whole capillary pathway. These changes in SHRSP seemed unfavorable for oxygen supply to ventricular tissues. To minimize the effects of the adverse changes, the ratio of the capillary to myocyte number increased markedly. The proportion of arteriolar capillaries increased and the venular proportion decreased.

Animals↗

Effects of chronic hypoxia and endurance training on muscle capillarity in rats.

Skeletal muscle capillarity expressed as capillary density (CD), and number of capillaries per fibre (C/F), as well as the mean fibre cross-sectional area (FCSA), were determined in the extensor digitorum longus (EDL), plantaris (PLA) and soleus (SOL) muscles of four groups of eight rodents trained on a swimming exercise programme (T) or maintained sedentary (S), at sea level (SL) or at simulated altitude (HA), barometric pressure 61.7 kPa (463 torr) for 12 weeks. It was shown that both HA exposure and endurance training decreased body and skeletal muscles weights (P less than 0.001). However, neither HA exposure nor endurance training induce any variation in relative importance in the skeletal muscle mass. Altitude exposure and endurance training had increasing effects on CD in all muscles studied (P less than 0.001). This study confirms the fact that altitude exposure has no direct effect on capillary development. On the other hand, the capillary supply of the several slow- and fast-twitch skeletal muscles studied is increased by endurance training. This real enhancement in capillary network is ascertained by an increase in the C/F ratio (+7%, +26%, +16%, in PLA, EDL, and SOL muscles, respectively at sea level, and +19.5%, +30%, and +14% respectively at HA). These results indicate that the effects of chronic exercise on skeletal muscle capillarity estimated by the C/F ratio, are greater in an hypobaric environment than in a SL environment.

Altitude↗

Changes in soleus muscle capillarity, oxidative capacity and fiber composition in rats recovering from hyperthyroidism.

Soleus muscle oxidative capacity, fiber composition and capillarity were studied in rats that were injected with 300-400 micrograms/kg of triiodothyronine (T3) every other day for 28 days and then left to recover for 4, 8, 14, 21 or 28 days. The activities of cytochrome c oxidase and citrate synthase and the capacity to oxidize pyruvate plus malate of muscle homogenates were 40, 53 and 21% higher than control values at the end of T3 administration. The activity of citrate synthase and the capacity to oxidize pyruvate plus malate decreased rapidly after discontinuing T3 administration, reaching values below those of base line controls in 14 days, but were not different than controls at 21 days. The activity of cytochrome c oxidase decreased more slowly, reaching base line values 28 days after discontinuing treatment with T3. Fiber composition was studied in cross-sections treated to demonstrate ATPase activity after acid pre-incubation. Three fiber types were present in the soleus of control animals: Type 1 with a strong ATPase reaction (86%), type II a with a weak ATPase reaction (12%) and a small proportion of type IIc with intermediate ATPase reaction (2%). After 28 days of T3 administration the proportion of type I fibers was significantly reduced (74%) while that of IIc was higher (18%). Fiber composition returned to normal between 21 and 28 days after T3 treatment was discontinued. Muscle capillarity was increased by T3 administration. Values of capillary density or capillary to fiber ratio at a given fiber cross sectional area were approximately 30% higher than controls at the end of T3 treatment and remained high until 21 days after discontinuing T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Successful prediction of immediate effects of undernutrition throughout the brain growth spurt on capillarity and synapse-to-neuron ratio of cerebral cortex in rats.

Based on the hypothesis that undernutrition depresses the growth rate of all processes in brain contemporaneous with it to the same extent (Peeling & Smart, 1994), specific predictions were made regarding the effect of undernutrition on two quite different facets of anatomical development within visual cortex. It was predicted that severe undernutrition during the suckling period would leave capillarity unaffected, but would result in a deficit in synapse-to-neuron ratio of similar magnitude to that in brain weight. At birth rat pups were fostered and either well fed to 30 days or undernourished to the same age by underfeeding their foster mothers. Rats were killed at 30 days by perfusion with glutaraldehyde. Visual cortex was dissected out for quantitative histological study. The number of capillary profiles per unit area of section and the area of each profile were assessed with an image analysis system. Quantitative characteristics of the neuron and synapse populations were estimated by light and electron microscopy respectively. Undernutrition resulted in a 21% deficit in brain weight, and a 22% deficit in the number of synapses per neuron. Capillarity, expressed as the fraction of section area occupied by capillary lumen, appeared completely indifferent to nutrition. However, fewer capillary profiles were found per unit area of section in growth-restricted samples, and the profiles which were present were, on average, larger. Neuron density was elevated by 19% in the undernourished group. These findings are in good agreement with the hypothesis.

Animals↗

Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis.

Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.

Adult↗

Volume overload hypertrophy elicited by cold and its effects on myocardial capillarity.

Capillarity and fiber cross-sectional areas were measured in the hearts of guinea pigs exposed to cold early during growth. Twelve male guinea pigs were kept at 5 +/- 1 degrees C for 4-18 weeks. Hearts were perfusion fixed via the aorta with a 2.5% glutaraldehyde, 1% formaldehyde-buffered solution, blocks were cut from left (LV) and right (RV) ventricles, post-fixed in OsO4, dehydrated and embedded in Spurr medium. Blocks were cut transversely to fiber orientation, 0.5 micron thick, stained with Toluidine Blue and photographed at 400 x. Heart weights, number and location of capillaries and fiber cross-sectional areas (FCSA) were measured in cold-acclimated animals and in normothermic controls. Growth rates for all guinea pigs were similar. Acclimation to cold caused modest LV and RV hypertrophy. The greater LV weight seemed due to longer fibers of normal FCSA, whereas the greater RV weight was due to larger FCSA. Capillary density, capillary-to-fiber ratio and number of capillaries around the fibers were similar in the two groups of animals. Mean and maximal diffusion distances in cold-acclimated animals were not different from controls. Thus the myocardial hypertrophy induced by chronic volume overload was fully compensated for by increases in capillarity commensurate with increases in fiber girth.

Acclimatization↗

Fiber capillarization in flight muscle of pigeons native and flying at altitude.

We examined structural characteristics for fiber O2 supply in the highly aerobic flight muscle of 5 pigeons (Columbia livia; body mass 223--317 g) native and actively flying at altitude (La Paz, Bolivia; 3750 m). Whereas deep sites were significantly more aerobic and highly vascularized than superficial in altitude (A) but not sea-level (SL) group, both sites showed a number of similarities between the two groups. The cross-sectional area of aerobic fibers (> or = 90% of fiber number) linearly increased with body mass (r 0.84; P < 0.0005) but was not smaller in A for their body mass, and there was no reduction in the size of glycolytic fibers compared to SL. The relationships between fiber capillarization and the sectional area of aerobic fibers in transverse sections or mitochondrial volume density were not altered in A compared to SL. The results indicate that the factors which determine the relationships between fiber capillarization and ultrastructure in the muscles were not altered by the adaptation to altitude. Differences between samples were related to the relative sectional area of aerobic fibers and mitochondrial volume density, not the chronic exposure to altitude.

Altitude↗

Capillarity and oxygen diffusion distances of the soleus muscle of guinea pigs and rats. Effects of hyperthyroidism.

The relationship between capillarity and oxidative capacity in the soleus muscle of rats and guinea pigs injected with triiodothyronine (T3) or with saline for up to 4 weeks was studied. The rats' soleus weight and FCSA were not affected by T3, but the guinea pigs that received T3 had smaller muscle weight and FCSA than the controls. The activities of cytochrome c oxidase and citrate synthase were significantly (41 and 65%) higher in the T3 than in the control rats. T3 administration did not affect the activities of these enzymes in the soleus of the guinea pigs. Capillary density (CD) was higher in T3 rats (892 +/- 80 vs 622 +/- 54 caps/mm2), and in T3 guinea pigs (1219 +/- 95 vs 739 +/- 142 caps/mm2). The higher CD in T3 rats was due to growth of new microvessels, while in the T3 guinea pigs it was due to a reduction in FCSA. Mean and maximal diffusion distances evaluated by the closest individual method were reduced by 2.02 and 3.37 microns in rats, and by 3.73 and 6.16 microns in guinea pigs. The magnitude of the reduction in diffusion distances brought about by the increased capillary density was partially offset by a concomitant change in the capillary arrangement from an ordered (hexagonal), towards a random distribution. These results seem to indicate that skeletal muscle capillarity is not necessarily determined by the oxidative capacity of the fibers.

Adenosine Triphosphate↗

Muscle capillarity in chicks following hypoxia.

1. Muscle capillarity was examined in chicks exposed to normobaric hypoxia with and without increased workload. 2. Capillarity was higher in the lateral head of the gastrocnemius, but not in the other muscles examined. Increased workload did not contribute to the effects of hypoxia. 3. Thus, hypoxia served as a stimulus for the development of new capillaries in muscle containing twitch fibers, but not in muscle containing tonic fibers.

Analysis of Variance↗

Skeletal muscle fiber composition and capillarization in patients with chronic heart failure: relation to exercise capacity and central hemodynamics.

Patients with chronic heart failure have structural and metabolic changes in skeletal muscle, which may be of importance for symptomatology. The origin of these changes are still unknown. The relationship between fiber composition and capillarization in skeletal muscle with exercise capacity and central hemodynamic variables was examined. Biopsies from the lateral vastus muscle were taken in 12 patients with chronic heart failure. Samples from eight normal subjects served as control samples. All patients underwent maximal exercise tests. Central hemodynamic variables were measured during exercise in five patients. The patients had a higher percentage of type II B fibers (P = .03) and fewer capillaries per fiber (P = .02) than the controls subjects. VO2 max correlated with the percentage of type I fibers, whereas the correlation with the type II A fibers was inverse. Cardiac index and pulmonary capillary wedge pressure at submaximal and maximal exercise were related to fiber type composition and relative fiber areas. Skeletal muscle fiber type composition and capillarization was changed in patients with chronic heart failure. These changes might influence exercise capacity. There were relationships between central hemodynamic variables and skeletal muscle changes. What the cause and effects were need further investigation.

Aged↗

Intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia are highly capillarized.

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP; ie, cryptogenic fibrosing alveolitis of mural type, CFA) are clinically and histologically distinguishable interstitial lung diseases. Both contain intraluminal lesions of newly formed fibromyxoid connective tissue. In BOOP, the fibromyxoid lesions are susceptible to complete reversal, but in UIP they are supposed to participate in the remodeling of the interstitium. Our hypothesis was that capillarization of the intraluminal fibromyxoid lesions is more frequent in BOOP compared with UIP. In this study, we stained diagnostic thoracoscopic or open lung biopsy specimens of patients with BOOP (n = 9) and UIP (n = 10) with antibodies against human laminin, von Willebrand factor, and CD34 to reveal the microvasculature of intraluminal fibromyxoid lesions. Our results show that in BOOP there is abundant capillarization in the newly formed intraluminal fibromyxoid lesions often reminiscent of granulation tissue. The mean number of capillaries per area unit (mm2) was 107 +/- SD 74 in samples stained for laminin, 103 +/- SD 46 for von Willebrand factor, and 63 +/- SD 36 for CD34. In marked contrast, in UIP, the corresponding accounts were significantly lower, being 14 +/- SD 15 for laminin (P < .003), 11 +/- SD 14 for von Willebrand factor (P < .001) and 6 +/- SD 6 for CD34 (P < .001). The intraobserver (P < .001) and interobserver correlations (P < .002) were highly significant, showing that our results are reproducible. We conclude that the content and nature of the newly formed intraluminal connective tissue, for example, in the form of vascular growth factors, are different in BOOP and in UIP, and this partly leads to the different clinical course of these diseases.

Adult↗

Bilateral iridocyclitis with retinal capillaritis in juveniles.

PURPOSE: The authors present clinical features of 18 juvenile patients with a new type of uveitis termed bilateral iridocyclitis with retinal capillaritis (BIRC). METHODS: The authors reviewed medical records of 18 consecutive patients who showed bilateral iridocyclitis with retinal capillary leakage but no systemic manifestations during an 11-year period from January 1985 to December 1995. RESULTS: Twelve of the 18 patients were female and the age at onset ranged from 9 to 17 years old. All patients had many cells in the anterior chamber and anterior vitreous, together with mutton fat keratic precipitates. Fluorescein angiography showed leakage from the optic disc and retinal capillaries, mainly in the midperiphery, which corresponded to retinal cloudiness. Macular edema was minimal, and all patients maintained good vision. The inflammation responded well topical, oral, and intravenous administration of corticosteroids, the choice of which was based on the extent of retinal inflammation. Human leukocyte antigen (HLA)-DR6 and HLA-Cw7 were associated significantly with the presence of BIRC (chi square test, P < 0.0001). CONCLUSIONS: Bilateral retinal capillaritis affecting capillaries in various areas of the retina and overlying retinal cloudiness with no distinct lesions are unique to these patients. Fluorescein angiography is essential for diagnosis of BIRC.

Acute Disease↗

Observing capillarity in hydrophobic silica nanotubes.

The development of template-synthesized silica nanotubes has created a unique opportunity for studying confined fluids by providing nanometer-scale containers in which the inner diameter (i.d.) and surface chemistry can be systematically and independently varied. An interesting question to be answered is the following: do solvents wet nanometer-scale tubes in the same way they wet ordinary capillaries? To answer this question, we have conducted studies to explore the wettability of the hydrophobic interiors of individual nanotubes. In these studies, single nanotubes with i.d.'s of either 30 or 170 nm were investigated over a range of water/methanol mixtures. These studies provide a direct route for comparing wetting phenomena in nanotubes with conventional macroscopic theories of capillarity. Our observations reveal four important aspects of capillary wetting in the 30-170 nm regime, a size range where the application of the Young-Laplace theory has not been experimentally investigated for hydrophobic pores. They are (i) a sharp transition between wetting and nonwetting conditions induced by addition of a cosolvent, (ii) invariance of this transition between nanotubes of 30 and 170 nm pore diameter, (iii) failure of the Young-Laplace equation to accurately predict the cosolvent's (methanol) mol fraction where the transition occurs, and (iv) reversibility of the observed wetting. The first two aspects conform to conventional capillarity (Young-Laplace), but the latter two do not. These measurements were complemented with ensemble experiments. The difference between theory and experiment is likely due to reliance on macroscopic values of contact angles or to liquid-phase instability within the hydrophobic pore.

Journal Article↗

The effect of aging on skeletal muscle capillarization in a murine model.

Capillarization of skeletal muscle has been reported to be both maintained and reduced with advancing age. This conflict may represent methodological differences between biopsy studies. We have examined capillarization throughout two muscles, soleus and extensor digitorum longus (EDL), from a well-established colony of aging mice, and related this to fiber number (C/F ratio) and type. Labeling of muscle capillaries was performed with the biotinylated Griffonia (Bandeiraea) simplicifolia lectin (GSL 1) using immunochemistry. The results showed a significant increase in the C/F ratio in the aged mice when compared with the younger (6-month mice soleus = 1.296, 95% CI 1.226-1.366 vs 28-month mice soleus = 1.530, 95% CI 1.488-1.572, p <.001; 6-month mice EDL = 0.881, 95% CI 0.751-1.011 vs 28-month mice EDL = 1.124, 95% CI 1.028-1.220, p = .017). These differences could not be accounted for by changes in fiber type but may reflect loss of fibers. Alternatively, there may be increased angiogenic drive or a failure of downregulation of angiogenesis.

Aging↗

Wegener's granulomatosis presenting with massive pulmonary hemorrhage and capillaritis.

The typical lesions of Wegener's granulomatosis in the lung consist of necrotizing granulomatous inflammation associated with a necrotizing vasculitis. We report an unusual case in which massive pulmonary hemorrhage was the initial manifestation. An open-lung biopsy showed intraalveolar hemorrhage and a necrotizing capillaritis, but no granulomas and no vasculitis involving arteries or veins. The diagnosis of Wegener's granulomatosis was established only at autopsy, when necrotizing granulomas and vasculitis were found. This case emphasizes that Wegener's granulomatosis should be considered in the differential diagnosis of pulmonary hemorrhage and necrotizing capillaritis.

Capillaries↗

Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat.

OBJECTIVES: To investigate whether combined treatment with lisinopril, an angiotensin-converting enzyme (ACE) inhibitor and exercise training would have an additive effect in enhancing the capillary supply of the left ventricular (LV) myocardium in spontaneously hypertensive rats (SHR). DESIGN: Twelve-week-old male SHR were divided into four groups (10-12 each): sedentary, sedentary treated with lisinopril (15-20 mg/kg per day by gavage), exercise trained, and exercise trained while treated with lisinopril. Exercise training consisted of 1 h a day/5 days a week of running on a treadmill. METHODS: After 10 weeks of experimental protocols, capillary surface density and length density were sterologically determined in 1 mum thick LV tissue samples from perfuse-fixed hearts. RESULTS: Lisinopril significantly reduced systolic blood pressure (SBP) and LV mass in the sedentary with lisinopril and exercise trained with lisinopril groups but did not affect the heart rate (HR). Exercise training did not reduce SBP or LV mass, but significantly reduced HR in the exercise trained and exercise trained with lisinopril groups. Lisinopril treatment (sedentary with lisinopril), exercise training (exercise) and their combination (exercise trained with lisinopril) significantly increased myocardial capillary surface area density by 26, 38 and 65% and length density by 38, 48 and 67%, respectively. CONCLUSION: Lisinopril administration and exercise training independently enhanced myocardial capillarization through a reduction of myocardial mass and stimulation of angiogenesis, respectively. A combination of the two treatments enhanced myocardial capillarization more than either intervention alone. This may aid in the restoration of the normal nutritional status of cardiac myocytes compromised by the hypertrophic state of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle.

The effect of intense training on endothelial proliferation, capillary growth and distribution of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was examined in human skeletal muscle. Two intermittent knee extensor training protocols (at approximately 150% (Study 1) versus approximately 90% (Study 2) of leg (O(2) max)) were conducted. Muscle biopsies were obtained throughout the training periods for immunohistochemical assessment of capillarization, cell proliferation (Ki-67-positive cells), VEGF and bFGF. In Study 1, microdialysis samples were collected from the trained and untrained leg at rest and during exercise and added to endothelial cells to measure the proliferative effect. After 4 weeks of training there was a higher (P < 0.05) capillary-to-fibre ratio (Study 1: 2.4 +/- 0.1 versus 1.7 +/- 0.1) and number of Ki-67-positive cells (Study 1: 0.18 +/- 0.05 versus 0.00 +/- 0.01) than before training. Neither the location of proliferating endothelial cells nor capillarization was related to muscle fibre type. The endothelial cell proliferative effect of the muscle microdialysate increased from rest to exercise in both the untrained leg (from 262 +/- 60 to 573 +/- 87% of control perfusate) and the trained leg (from 303 +/- 75 to 415 +/- 108% of perfusate). VEGF and bFGF were localized in endothelial and skeletal muscle cells and training induced no changes in distribution. The results demonstrate that intense intermittent endurance training induces capillary growth and a transient proliferation of endothelial cells within 4 weeks, with a similar growth occurring around type I versus type II muscle fibres.

Adult↗

Effects of long-term, high-altitude hypoxia on the capillarity of the ovine fetal heart.

To determine the effect of chronic hypoxia on myocardial capillarity, we exposed pregnant ewes to an altitude of 3,820 m from day 30 to day 139 of gestation and compared the fetus to low-altitude (approximately 300 m) controls. We hypothesized that capillarity would increase in the hypoxic myocardium to optimize oxygen and metabolite flux to hypoxic tissues. Fetal hearts were fixed by retrograde aortic perfusion and processed for microscopy and stereological evaluation. Fiber cross-sectional area and capillary density were measured and standardized to sarcomere length. Capillary volume density and capillary diameter were measured, capillary-to-fiber ratio and capillary length density were calculated, and the capillary anisotropy coefficient was obtained from a table of known values. Capillary-to-fiber ratio, capillary volume density, and the capillary anisotropy coefficient were not different between hypoxia and control groups. Capillary diameter was significantly larger in the right compared with the left ventricle of hypoxic but not control hearts; fiber cross-sectional area tended to be larger in the right ventricle of both groups, but this was not significant. As a result of larger fiber size, capillary density and capillary length density were significantly smaller in the right ventricle of hypoxic but not control fetal hearts. Contrary to our hypothesis, the ovine fetus does not show morphological adaptation in the myocardium after approximately 109 days of high-altitude hypoxic stress.

Altitude↗