Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle

Rat extensor digitorum longus muscles were overloaded by stretch after removal of the synergist tibialis anterior muscle to determine the relationship between capillary growth, muscle blood flow, and presence of growth factors. After 2 wk, sarcomere length increased from 2.4 to 2.9 micrometers. Capillary-to-fiber ratio, estimated from alkaline phosphatase-stained frozen sections, was increased by 33% (P < 0.0001) and 60% (P < 0.01), compared with control muscles (1.44 +/- 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with any changes in mRNA for basic fibroblast growth factor (FGF-2) or its protein distribution. FGF-2 immunoreactivity was present in nerves and large blood vessels but was negative in capillaries, whereas the activity of low-molecular endothelial-cell-stimulating angiogenic factor (ESAF) was 50% higher in stretched muscles. Muscle blood flows measured by radiolabeled microspheres during contractions were not significantly different after 2 or 8 wk (132 +/- 37 and 177 +/- 22 ml. min-1. 100 g-1, respectively) from weight-matched controls (156 +/- 12 and 150 +/- 10 ml. min-1. 100 g-1, respectively). Resistance to fatigue during 5-min isometric contractions (final/peak tension x 100) was similar in 2-wk overloaded and contralateral muscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with 77% in contralateral muscles and 67% in controls. We conclude that increased blood flow cannot be responsible for initiating expansion of the capillary bed, nor does it explain the reduced fatigue within overloaded muscles. However, stretch can present a mechanical stimulus to capillary growth, acting either directly on the capillary abluminal surface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.     

Flow modulates endothelial regulation of smooth muscle cell proliferation: a new model

BACKGROUND: With a co-culture model, we have previously demonstrated that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that the EC stimulation of SMC proliferation was effected by shear stress. METHODS: Bovine SMCs were cultured on a thin semipermeable membrane either alone or opposite ECs in co-culture (SMC/EC). A novel parallel-plate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were determined after 24 hours' exposure to 0, 1, or 10 dynes/cm2 of shear stress. RESULTS: SMC proliferation decreased significantly from 362 +/- 65 cpm/microgram DNA (control, mean +/- SEM) to 68 +/- 43 cpm/microgram (1 dyne/cm2) and 99 +/- 18 cpm/microgram (10 dynes/cm2)(P < .05). EC proliferation after flow decreased as compared with no-flow controls 71 +/- 15 cpm/micrograms DNA (control, mean +/- SEM) to 29 +/- 5 cpm/microgram (1 dyne/cm2) and 21 +/- 4 cpm/microgram (10 dynes/cm2)(P < .05). CONCLUSIONS: In a model designed to study SMC/EC interactions in a flow environment, it was seen that EC exposure to shear stress alters the growth characteristics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior.     

Regional, developmental, and cell cycle-dependent differences in mu, delta, and kappa-opioid receptor expression among cultured mouse astrocytes

Of all skeletal muscles examined in the rat, the spinotrapezius (S) and diaphragm (D) have the closest fiber-type composition. However, their oxidative capacities differ by two- to threefold. We have developed an intravital microscopy preparation to study diaphragm microcirculation in vivo. Using this preparation and the standard spinotrapezius model first described by S. D. Gray (1973, Microvasc. Res. 5, 395-400), we tested the hypothesis that pronounced microcirculatory differences would exist between these two muscles as a function of their disparate oxidative capacities. The lineal density of all capillaries in the spinotrapezius was 33.6 +/- 1.5 compared to 65.1 +/- 3.3 capillaries/mm in the diaphragm (P < 0.001). In the diaphragm compared with the spinotrapezius muscle, a significantly (P < 0.05) greater proportion of capillary countercurrent flow (D, 29 +/- 6% vs 8 +/- 6%) existed. Within both muscles, there was a similar proportion of capillaries supporting red blood cell (RBC) flow (S, 89 +/- 7% vs D, 92 +/- 2%). However, the diaphragm supported significantly (P < 0.001) greater intracapillary RBC velocities (D, 302 +/- 11 vs S, 226 +/- 9 micron/s) and fluxes (D, 33.4 +/- 1.1 vs S, 19.2 +/- 2.1 cells/s) compared with the spinotrapezius. Capillary "tube" hematocrit was greater (P = 0.01) in the diaphragm (0.32 +/- 0.02) than in the spinotrapezius (0.22 +/- 0.03) muscle. These data demonstrate that microcirculatory flow characteristics in resting muscle can be regulated independent of muscle fiber-type composition and may be related to muscle oxidative capacity.     

Response of spinal cord capillaries of white rats to exposure to noise

Changes in diameters of blood capillaries of the white rat spinal cord, peculiar changes in volume and metabolic surface of capillaries in the cervical part of the spinal cord were studied under the effect of noise (90-100 db, 2 h daily, for 2, 4 and 8 weeks). Restorative period was started in 4 and 16 weeks after the experiment was stopped. A considerable narrowing of the capillary lumen was found in the test animals comparing to the normal state. The investigations performed demonstrated that the quantitative changes in the capillary indices depended on the noise duration and were considered as gradual development of adaptive-compensatory reaction of the vascular system to noise. The changes mentioned, however, were not irreversible, as during the restorative period a gradual widening of the capillary diameters was observed. Nevertheless, the "rest" lasting for 16 weeks was not enough for the capillary bed of the spinal cervical part to restore its normal indices.     

A single glucose transporter configuration in normal primate brain endothelium: comparison with resected human brain

Cellular distribution of the Glut1 glucose transporter in normal primate brains was analyzed by immunogold electron microscopy. Two configurations of endothelial Glut1 glucose transporter (high and low density capillaries) have been found in resections of traumatically injured and epileptogenic human brain; the objective of the present study was to ascertain whether these same 2 capillary populations, expressing high and low glucose transporter densities, were the common configuration in normal brain. The relative numbers of Glut1 glucose transporter-associated gold particles on luminal and abluminal endothelial cell membranes were determined within the cerebral cortex of several normal, nonhuman primates. Low Glut1 densities were seen in brain endothelia of both the rhesus and squirrel monkey cortex, with slightly greater quantities of Glut1 in vervet monkey cortices. The Glut1 transporter was most highly expressed in the baboon cortex, approaching the concentrations seen in human brains. In the rhesus, squirrel, and vervet monkeys, Glut1 concentrations were greater on the abluminal than luminal capillary membranes. In contrast, mean luminal membrane Glut1 concentrations were greater in baboons, resembling the distribution seen in the human brain. Brain regional differences in transporter concentration were seen in comparing membrane densities in the baboon cortex (approximately 15 Glut1-gold particles per micrometer), hippocampus (approximately 12 Glut1 gold particles per micrometer), cerebellum (approximately 6 Glut1-gold particles per micrometer), and retinal microvasculature (approximately 20 Glut1-gold particles per micrometer). We conclude that a single, uniform Glut1 distribution characterizes brain capillaries of normal nonhuman primates, and hypothesize that the presence of high and low density glucose transporter endothelial cells (seen in human traumatic injury and seizure resections) represents a pathologic response to brain insult.     

Habituation of facial muscle responses to repeated food stimuli

The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3 mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5 to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and chronic implantation were obtained in 52 stented coronary segments of 18 dogs. Three hearts with 8 stented coronary segments were harvested after 24 hr, 3 hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15 stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments were harvested at 24 weeks post-deployment. There were no procedural complications, deaths, or acute vessel closures. The average lumen diameter of the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P < 0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent of stenosis was <30% in all animals. Histologically, a peak of inflammation was visible at 2 weeks; however, the extent of luminal narrowing reached its peak at 8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of intimal thickening remained relatively constant throughout the different time points (<200 microm). Overall, these data suggest that constrictive remodeling within the stented segment occurs at 8 weeks in this animal model. The later increase of the stented segment dimensions as well as higher net gain at 24 weeks compared to 8 weeks after deployment suggests that this constriction is a transitory phenomenon.     

The prevention and treatment of postoperative thrombosis of the deep veins of the lower extremities (II. Treatment)

Defining the most appropriate conditions for strengthening the retention of endothelial cells (ECs) by small-diameter prosthetic endothelialized grafts is indispensable to their clinical application. The incubation time after seeding is one of the most important factors in EC retention. The effects of different postincubation times (0, 2, 4, 8, 16, 24, and 36 hr) on EC monolayers on two different types of graft, fibronectin-coated expanded polytetrafluoroethylene (ePTFE) and collagen-coated knitted Dacron grafts (4 mm x 5 cm) were examined. In situ counting of ECs on the grafts was performed by light microscopy. The percentage cell retention was calculated by dividing the cell counts for grafts exposed to pulsatile flow for 90 min by those for control grafts. To characterize the EC coverage of the grafts, scanning electron microscopy was also performed. The average cell density of control grafts ranged from 5.59 +/- 1.1 to 6.69 +/- 1.5 x 10(4) cells/cm2 and did not differ according to the kind of graft or incubation time. The knitted Dacron grafts showed the maximal cell retention (88 +/- 5%) after incubation for 8 hr, whereas ePTFE grafts did so after 24 hr (83 +/- 6%). Scanning electron microscopic examination after incubation for 8 hr revealed that the density of human ECs on the surfaces of ePTFE and Dacron grafts differed, although there was no morphological difference between the ECs on the two types of graft. Knitted Dacron grafts achieved a high percentage retention in a shorter time than ePTFE grafts.     

Improved adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in a canine model

PURPOSE: A significant limitation to using genetically modified endothelial cells (ECs) to seed prosthetic grafts before implantation has been poor cell adherence to the graft lumen. Methodologic changes to improve cell adherence were evaluated in a canine carotid interposition graft model using 4 mm interior diameter expanded polytetrafluoroethylene. METHODS: ECs harvested from external jugular veins were grown in culture, with 80% of the cells from each culture transduced by incubation with an LXSN-type retroviral vector carrying a gene for human prourokinase and a neomycin resistance gene for selection in antibiotic G418. Control grafts had passive luminal coating with fibronectin and were seeded with transduced ECs immediately after G418 selection; these grafts were incubated for 2 days before implantation. Experimental grafts had fibronectin forcefully squeezed through the interstices and were seeded with ECs that had recovered in culture for 5 days after G418 selection; these grafts were incubated for 4 days before implantation. For each control (n = 9) and experimental (n = 12) graft, a graft prepared in the same fashion but seeded with the remaining autologous nontransduced cells was placed in the contralateral carotid artery. Grafts were explanted after 30 days and were evaluated for patency, thrombus-free surface area, and cell-free surface area. RESULTS: No significant differences in patency rates were seen between any groups. The thrombus-free surface area was improved for experimental grafts (90%) compared with control grafts (76%), but this improvement did not achieve statistical significance. The cell-free surface area for transduced cells on experimental grafts was 65% compared with 96% for control grafts (p = 0.021) and was comparable with that for nontransduced cells on both control grafts (62%) and experimental grafts (51%; p = 0.201). CONCLUSIONS: Adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in an in vivo physiologic flow model is significantly improved when cells have a more prolonged recovery from G418 selection, when the graft lumen is more uniformly coated with fibronectin before EC seeding, and when seeded grafts are left longer in culture before implantation to develop cell lining stability. The short-term patency rate of these seeded grafts is not affected by increased cell retention; long-term graft patency data and luminal healing require further evaluation.     

Autonomic regulation of nasal vessels during changes in body position

The effects of postural changes on nasal airflow and nasal capillary blood flow were investigated in 15 healthy volunteers. Measurements were performed following nasal application of saline solution (control), the alpha-1 receptor antagonist prazosin, the alpha-2 receptor antagonist yohimbine, and after application of both prazosin and yohimbine. Nasal airflow in the control experiments did not significantly differ in the upright (362 +/- 166 ml/s), dorsally recumbent (350 +/- 167 ml/s) and 70 degrees head down position (311 +/- 167 ml/s). Following application of prazosin, nasal airflow was reduced to 223 +/- 121 ml/s in the upright position. Prazosin treatment significantly reduced nasal airflow to 177 +/- 111 ml/s when subjects were placed in dorsally recumbent positions and to 117 +/- 104 ml/s in 70 degrees head down positions (P < 0.001). Following application of yohimbine, nasal airflow remained stable when subjects were turned from upright (348 +/- 165 ml/s) to supine position (352 +/- 186 ml/s), whereas it was reduced to 199 +/- 137 ml/s in the head-down position. Application of both prazosin and yohimbine significantly increased nasal capillary blood flow in laser Doppler flowmetry measurements (P < 0.05). Changes in body position with or without application of the active drugs did not alter nasal capillary blood flow. These findings suggest that nasal congestion due to increased filling pressure in nasal capacitance vessels following postural changes is mainly prevented by alpha-1 adrenergic mechanisms.     

Application of coacervated alpha-elastin to arterial prostheses for inhibition of anastomotic intimal hyperplasia

Prevention of anastomotic intimal hyperplasia (AIH) requires inhibition of the migration of smooth muscle cells (SMCs) and promotion of endothelial cell (ECs) growth from the native arterial wall. We investigated the effect of coacervated alpha-elastin on migration of SMCs and ECs in vitro. SMCs and ECs were prepared from porcine aortic media and endothelium. Coacervated alpha-elastin was coated and cross-linked around the perimeter of each 1 cm diameter center of a well in a 12 well plate. SMCs and ECs were placed and cultured within the center of each well. The migration of SMCs and ECs on coacervated alpha-elastin was assayed on the second, third (10 mg/ml), or fourth day (0.1, 1.0, 10.0 mg/ml) of cultivation by measuring the area of migration from the 1 cm diameter center. Coacervated alpha-elastin was then coated and cross-linked on a Dacron graft using 1% glycerol polyglycidyl ether (GPGE) and examined with scanning electron microscopy to determine the feasibility of graft coating. SMC migration was significantly inhibited dose dependently over time (p < 0.005), e.g., 0.1 mg/ml (45.4% +/- 2.7%: % of MES [pH 5] and 1% GPGE without alpha-elastin), 1.0 mg/ml (32.0% +/- 1.4%), 10.0 mg/ml (8.3% +/- 2.9%). EC migration (90.7% +/- 6.2%: p = ns) was not inhibited by 0.1 mg/ml of coacervated alpha-elastin. Cross-linked coacervated alpha-elastin was coated on a dacron graft uniformly. Incorporation of coacervated alpha-elastin into the structure of arterial prostheses offers the possibility of inhibition of SMC hyperplasia without inhibition of EC formation.     

Local progression of atherosclerosis after optimal directional atherectomy. Endocoronary ultrasonography of 17 patients

In vivo endovascular ultrasonography has confirmed the extension of atheroma to angiographically normal segments. The authors set out to determine by endocoronary ultrasonography if the introduction of the atherotome changed the intimal thickness 20 mm proximal and distal to the site treated. The area circumscribed by the external elastic layer (EEL) and the surface area of the lumen was measured in 17 patients: 1) before atherectomy; 2) after atherectomy; 3) at control 6 months later. Atherectomy immediately increased the luminal area at the site dilated from 1.9 + 0.9 to 8.1 +/- 2mm (p < 0.001). At the proximal segment, the surface area of the lumen was unchanged (mean + 0.6 +/- 1.5 mm2; p = 0.13). Similarly the procedure did not change the surface circumscribed by the EEL (mean + 0.8 +/- 3.2 mm2; p = 0.32) in this zone. The same results were observed at the distal site. At 6 months, the areas under the EEL and those of the lumen were unchanged at the unoperated sites. The mean of the differences (+/- 1 SD) for the area under the EEL was respectively -0.2 +/- 1.5 mm2 proximally and +0.7 +/- 2.5 mm2 distally. The means for the luminal area were 0.2 +/- 1 mm2 proximally and -0.01 +/- 1.1 mm2; distally. At the site of atherectomy, the luminal surface increased (+2.0 +/- 2.6 mm2; p < 0.01) as did the area under the EEL (+2.0 +/- 3.5 mm2; p < 0.05). This preliminary series shows no significant progression of atherosclerosis at the sites not affected by atherectomy.     

Mechanisms of luminal enlargement and quantification of vessel wall trauma following balloon coronary angioplasty and directional atherectomy

OBJECTIVES: The purpose of this study was to assess the dual action of lumen enlargement and vessel wall damage following either balloon angioplasty or directional atherectomy, using intracoronary ultrasound, and angioscopy. BACKGROUND: Differences in the mechanisms of action of balloon angioplasty and directional atherectomy may have a significant bearing on the immediate outcome and the restenosis rate at 6 months. METHODS: A total of 36 patients were studied before and after either balloon angioplasty (n = 18) or directional atherectomy (n = 18). Ultrasound measurements included changes in lumen area, external elastic membrane area and plaque burden. In addition, the presence and extent of dissections were assessed to derive a damage score. Angioscopic assessment of the dilated or atherectomized stenotic lesions was translated into semi-quantitative dissection, thrombus and haemorrhage scores. RESULTS: Atherectomy patients had a larger angiographic vessel size compared with the angioplasty group (3.55 +/- 0.46 mm vs 3.00 +/- 0.64 mm, P < 0.05); however, minimal lumen diameter (1.18 +/- 0.96 mm vs 0.85 +/- 0.49 mm) and plaque burden (17.04 +/- 3.69 vs 15.23 +/- 4.92 mm2) measurements did not differ significantly. As a result of plaque reduction, atherectomy produced a larger increase in luminal area than the angioplasty group (5.80 +/- 1.78 mm2 vs 2.44 +/- 1.36 mm2, P < 0.0001). Lumen increase after angioplasty was the result of 'plaque compression' (50%) and wall stretching (50%). Additionally, in both groups there was indirect angioscopic evidence of thrombus 'microembolization' as an adjunctive mechanism of lumen enlargement. Angioscopy identified big flaps in six and small intimal flaps in 11 of the atherectomized patients as compared with five and 12 patients in the angioplasty group. Changes in thrombus score following both coronary interventions were identical (0.72 +/- 3.42 points atherectomy vs -0.38 +/- 3.27 points balloon angioplasty, ns). CONCLUSIONS: Lumen enlargement after directional atherectomy is mainly achieved by plaque removal (87%), whereas balloon dilation is the result of vessel wall stretching (50%) and plaque reduction (50%). Despite the fact that the luminal gain achieved by directional atherectomy is twice that achieved with balloon angioplasty, the extent of trauma induced by both techniques seems to be similar.     

Osmotic water permeability of capillaries from the isolated spiral ligament: new in-vitro techniques for the study of vascular permeability and diameter

Perilymph is separated from blood by a barrier called the blood-labyrinth or blood-perilymph barrier in analogy to the blood-brain or blood-cerebrospinal fluid barrier. These barriers consist mainly of vascular endothelial cells. To characterize the blood-labyrinth barrier we developed in vitro techniques for the quantitative determination of the osmotic water permeability and for the determination of changes in the diameter of isolated inner ear capillaries. Both techniques rely on measurement of the velocity of marker red cells trapped in the lumen of capillaries. The velocity of marker red cells is a measure for the capillary permeability when a water flux across the capillary wall is induced by an osmotic gradient or a measure for a change in the capillary diameter. With these techniques the osmotic water permeability coefficient (Pf) and the pH sensitivity of isolated capillaries from the spiral ligament of the inner ear was determined. Pf at 23 degrees C was (1.49 +/- 0.17) 10(-3) cm/s at pH 7.4 and (1.61 +/- 0.23) 10(-3) cm/s at pH 6.8 (n = 12: mean +/- SEM: n = number of tissues). Pf at 37 degrees C was (2.26 +/- 0.23) 10(-3) cm/s at pH 7.4 and (2.35 +/- 0.17) 10(-3) cm/s at pH 6.8 (n = 13). No change in capillary diameter was observed when the pH of the interstitial fluid was lowered from pH 7.4 to 6.8. These data demonstrate that Pf and the capillary diameter of spiral ligament capillaries are pH independent and suggest that water crosses the blood-labyrinth barrier via an aqueous pathway. Further, these data suggest that the relatively low Pf is another characteristic shared by the blood-labyrinth and the blood-brain barrier.     

Ultrastructural study of capillary and myocytic changes in the masseter and heart of KK-Ay mice

We studied the capillaries and myocytes of masseter and cardiac muscles of diabetic KK-Ay mice, using light microscopy, transmission electron microscopy and scanning electron microscopy. The following changes were observed for diabetic masseters: capillary tortuosity, diversity of capillary caliber, endothelial cell swelling accompanied by luminal narrowing, widening of the pericapillary space and pericapillary fibrosis, and subsarcolemmal accumulation of myocytic mitochondria in areas adjacent to capillaries. In addition, attenuated capillary segments were largely covered by pericytes with profuse processes. In contrast, cardiac muscles of KK-Ay mice exhibited subsarcolemmal accumulation of myocytic mitochondria in areas contiguous to capillaries, and degenerative changes of myocytes such as disarrangement of myofilaments, disappearance of Z-bands and clustering of lipid-like vacuoles, although conspicuous changes of capillaries were not noted. Microvascular and myocytic changes described above may suggest the presence of microangiopathy and myopathy in the masseter and heart of KK-Ay mice.     

Adrenergic control of bicarbonate absorption in the proximal convoluted tubule of the rat kidney

The effects of norepinephrine and phenoxybenzamine on bicarbonate absorption in the rat proximal convoluted tubules were studied by simultaneous microperfusion of tubule and peritubular capillaries. Bicarbonate was determined by using a pH-sensitive membrane electrode system. The rates of bicarbonate absorption (JHCO3) were examined in the same proximal tubule before and after the addition of norepinephrine or phenoxybenzamine. When the proximal tubule was perfused with Ringer solution and peritubular capillaries were perfused with albumin Ringer solution, JHCO3 was 145 +/- 3.3 pEq/min X mm. Addition of 2 X 10(-6) mol/l norepinephrine to the capillary perfusate caused a 21% increase in JHCO3. Addition of 2 X 10(-6) mol/l phenoxybenzamine to the capillary perfusate caused a 12% decrease in JHCO3. Addition of both norepinephrine and phenoxybenzamine to the capillary perfusate caused a 19% decrease in JHCO3. However, there was no significant effect on JHCO3 observed when either norepinephrine or phenoxybenzamine was added to the luminal perfusate. These results suggest that adrenergic nerves participate in the regulation of renal tubular bicarbonate absorption through the direct action of norepinephrine on adrenergic receptors located at the basolateral side of the proximal tubule.     

Performance of small diameter synthetic vascular prostheses with confluent autologous endothelial cell linings

Autologous grafts are superior to their synthetic counter-parts for grafting arteries smaller than 6-mm diameter both in terms of acute thrombogenicity and chronic intimal hyperplasia. Endothelial cell (EC) coating of the blood contacting surface may reduce thrombogenicity of synthetic small diameter vascular prostheses. In this study, the survival of EC monolayers on synthetic 4-mm diameter arterial prostheses over short-term implantations (< or = 6 weeks) was examined. Graft types examined were expanded polytetra-fluoroethylene (ePTFE) and microporous polyurethane (PU). Lumenal coverage with ECs was achieved by culturing ovine ECs on prostheses treated by either physical adsorption or covalent binding of ovine fibronectin (Fn). An ovine carotid interposition model was used to examine the performance of EC coated ePTFE and microporous PU over implantation periods of 1, 3, and 6 weeks. Outcomes assessed at the end of each experiment were graft patency, area covered by ECs, and thrombus free surface area (TFSA). Fn concentration, cell density at the time of coating and prostacyclin production in vitro were similar for both graft types. Occlusion occurred more frequently in unseeded grafts compared with EC coated grafts over 3 and 6 week implantation periods; however, the difference was not significant (p = 0.099). In prostheses precoated with ECs, approximately 40-60% of the surface area remained covered with endothelial-like cells following the first postoperative week. Recovery of EC layers occurred rapidly thereafter with 80-90% coverage at 3 weeks. TFSA remained low in comparison to EC cover in these prostheses until between 3 and 6 weeks postoperatively, suggesting a lag phase in recovery of EC function of seeded cells. In contrast, EC cover of unseeded prostheses only achieved 10-30% at 3 weeks, primarily by pannus EC ingrowth from the adjacent artery. TFSA of unseeded grafts increased in direct proportion to EC cover over time suggesting that there was no lag phase in function of these ingrowing cells.     

Theory of gas exchange in the avian parabronchus

To understand the distribution of oxygen and carbon dioxide in the avian lung, a theoretical treatment of gas exchange in the parabronchus of the avian lung is described. The model is modified after Zeuthen (1942). In addition to bulk flow through the parabronchial lumen, diffusion through the air spaces of both the parabronchial lumen and air capillaries is treated. The relationship of PO2 and PCO2 within the blood capillaries, air capillaries, and parabronchial lumen to parabronchial blood flow and ventilation is graphically shown. The results indicate that the variations of PO2 and PCO2 along an air capillary are less than one torr under resting conditions. Removal of diffusion resistance within the air space of the air capillaries increases calculated parabronchial gas exchange by less than 0.1% at rest. At high or resting ventilation rates the partial pressure profile along the parabronchial lumen calculated considering bulk flow only agrees well with the profile calculated considering bulk flow and axial diffusion, but as the ventilation rate decreases there is increasingly large disagreement. Forward diffusion of O2 toward the parabronchus reduces pre-parabronchial PO2 and backward diffusion of CO2 from the parabronchus increases PCO2. Neglecting diffusion within the air spaces of both the lumen and the air capillaries increases calculated parabronchial gas exchange by less than 2% (CO2) or 6% (O2) at rest.     

Endothelin-A receptors mediate vasoconstriction of capillaries in the spiral ligament

The purpose of this study was to determine whether endothelin-1 (ET-1), endothelin-2 (ET-2) or endothelin-3 (ET-3) alter the vascular diameter of capillaries in the spiral ligament. Changes in vascular tone were measured in capillaries from the isolated spiral ligament in vitro. Capillaries were occluded on one end and opened on the other end. Red blood cells trapped in the capillaries served as markers for a luminal volume defined by the red cell itself, the capillary wall and the occluder. Movement of the red cell toward the open end was taken as evidence for vasoconstriction and movement of the red cell toward the occluder was taken as evidence for vasodilation. The inner diameter of the capillaries was 7.0 microm and decreased maximally by a factor of 0.8 in response to ET-1 and ET-2 (both 10(-8) M). Vasoconstriction induced by ET-1 and ET-2 was concentration-dependent in the range between 10(-12) and 10(-8) M whereas ET-3 (10(-8) M) had no effect. The EC50s for ET-1 and ET-2 were 1.2 x 10(-10) M and 1.4 x 10(-9) M, respectively. Thus, the potency order was ET-1 > ET-2 > ET-3. Vasoconstriction induced by ET-1 and ET-2 was completely inhibited by the competitive antagonist 10(-6) M BQ-123 (cyclic D-Asp-L-Pro-D-Val-L-Leu-D-Trp). Vasoconstriction induced by ET-1 or ET-2 continued for more than 1 min after removal of agonist from the perfusate. Rapid vasodilation of capillaries preconstricted by ET-1 was observed in response to 10(-3) M sodium nitroprusside. Sodium nitroprusside, however, had no significant effect on the vascular diameter of resting capillaries. These results demonstrate that capillaries in the spiral ligament can constrict and the endothelin-mediated vasoconstriction occurs via ET(A) receptors.     

The preferential mobilisation of C20 and C22 polyunsaturated fatty acids from the adipose tissue of the chick embryo: potential implications regarding the provision of essential fatty acids for neural development

The effects of 10 day clenbuterol administration on cardiac and skeletal muscle capillarities were studied, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary density, in young (10-week-old) and middle-aged (37-week-old) male Wistar rats. Rats of the treated groups were fed a diet containing 2 mg kg-1 clenbuterol hydrochloride. In both young and middle aged rats, clenbuterol treatment increased the body wt and the weights of the heart and hindlimb muscles. The mean fibre cross-sectional area was significantly increased after the treatment in the left ventricle, soleus, plantaris and both deep and superficial portions of gastrocnemius (P < 0.01). In the left ventricle, the total capillary density and the density of venular capillaries were decreased after the treatment in both young (9 and 13%, respectively) and middle-aged rats (10 and 11%, respectively). A decrease in total capillary density was also observed in all skeletal muscles examined. In both young and middle-aged rats, the capillary-to-fibre (C:F) ratio and the proportion of each capillary did not change after the treatment in both the left ventricle and skeletal muscles. Clenbuterol significantly decreased the activity of succinate dehydrogenase in all skeletal muscles examined (P < 0.01). These results suggest that clenbuterol increased the diffusion distance for oxygen in the left ventricle and skeletal muscles. These changes may reduce the oxygen supply to tissues and increase muscle fatigability.