Immunolocalization of type VIII collagen in vascular tissue

Type VIII collagen was first detected in the culture medium of aortic endothelial cells. Subsequently its synthesis by a number of other cell lines was demonstrated. Its presence in vascular tissue is reported here. It is a component of sheep aorta and carotid artery but could not be demonstrated in the jugular vein. It is principally localized in the subendothelial region but this can only be demonstrated after pretreatment of the tissue with proteases. Thus type VIII collagen is a constituent of blood vessels.     

Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load

We examined the role of the carotid chemoreceptors in the ventilatory response to changes in venous CO2 load in 12 awake sheep using a venovenous extracorporeal perfusion circuit and two carbon dioxide membrane lungs (CDML). Three of the sheep had undergone surgical denervation of the carotid bodies (CBD). In the nine intact sheep, as CO2 was removed from or added to the peripheral venous blood through the CDML under normoxic conditions, there was a linear relationship between the rate of pulmonary CO2 excretion (VCO2) and the resulting rate of ventilation over a VCO2 range of 0--800% of control, so that arterial PCO2 remained close to isocapnic. In contrast, in the three CBD sheep, the ventilatory response to changes in VCO2 was significantly decreased under normoxic conditions, resulting in marked hypercapnia. The results indicate that the carotid chemoreceptors exert a major influence on the ventilatory response to changes in venous CO2 load.     

Parotid secretion and associated efferent activity inhibited by pentagastrin in sheep

The inhibition of parotid secretion by pentagastrin increased with dose for jugular and carotid injections (0.01-0.16 micrograms/kg) in acute preparations of 3 sheep anesthetized with sodium pentobarbital. The intracarotid effect exceeded that for the jugular both in magnitude across all doses and in slope relating % inhibition to ln dose (p less than 0.005). The greater depression from carotid injections indicated that the effect was mediated in the head in response to higher pentagastrin concentrations at any dose level. In other experiments, both secretion and associated efferent activity in the parotid nerve were depressed more by carotid than jugular injections of pentagastrin, secretion being reduced by 27.2 vs. 12.1% and efferent activity by 43.2 vs. 20.6% respectively (p less than 0.025). These results indicate that gastrin in the circulation may be able to inhibit parotid secretion in sheep by acting directly on the central nervous system.     

Prostacycin production by arterialized autogenous venous grafts in dogs

Arteries are capable of producing significantly larger quantities of protacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI₂ released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. “Arterialized” vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid- stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF_1α) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.     

An angiographic study of the carotid arterial and jugular venous systems in the cat.

Standard techniques for performing carotid angiography in dogs and in man were adapted to the cat in order to study the vascularization of both intracranial and extracranial structures. Venous drainage was examined by venography of selected vessels. The carotid-cerebral and the vertebral-basilar arterial systems of the cat were studied, although no attempt was made to define the territory supplied by each system. In serial angiograms, vascularization of the rete mirabile conjugatum was visualized and distinct arterial and venous retia were delineated. Large facial veins were seen approximately one second after the intra-arterial injection of radio-contrast material. The early filling of the large facial veins appeared to be the result of an artery-to-venous shunt. Contrast material flowed posteriorly in these veins and drained into the venous rete. When contrast material was injected either into the sagittal sinus or retrograde in the external jugular vein, the internal jugular vein was visible in four of ten cats. This vessel drained blood directly from intracranial contents before anastomosis with the vertebral and external jugular veins.     

Progesterone in uterine and arterial tissue and in jugular and uterine venous plasma of sheep

Concentrations of progesterone in uterine and arterial tissue and in uterine and jugular venous plasma were determined. Blood was collected on Days 4 and 9 postestrus from the jugular vein and the first and last venous branches draining each uterine cornu; uterine tissue and arteries were subsequently collected. Progesterone was greater (p less than 0.05) in the cranial third than in the middle or caudal thirds of the uterine horn adjacent to the corpus luteum (CL)-bearing ovary or in any third of the contralateral horn. Progesterone in uterine arterial segments adjacent to the CL-bearing ovary was higher (p less than 0.05) than in contralateral segments. Progesterone was higher (p less than 0.05) in blood from the first venous branch of the cranial third of the uterine cornu adjacent to the ovary with the CL, than in the last branch of the caudal third, or contralateral horn, or in jugular blood. When oviductal veins were resected on Day 9 postestrus, progesterone in the first vein draining the cranial third of the uterine cornu adjacent to the CL-containing ovary was not different (p greater than 0.05) 48 h after resection than in the same vessel in the opposite horn or in jugular blood. We concluded that progesterone and other ovarian products may be delivered to the uterus locally.     

Plasticity of endothelial cells during arterial-venous differentiation in the avian embryo

Remodeling of the primary vascular system of the embryo into arteries and veins has long been thought to depend largely on the influence of hemodynamic forces. This view was recently challenged by the discovery of several molecules specifically expressed by arterial or venous endothelial cells. We here analysed the expression of neuropilin-1 and TIE2, two transmembrane receptors known to play a role in vascular development. In birds, neuropilin-1 was expressed by arterial endothelium and wall cells, but absent from veins. TIE2 was strongly expressed in embryonic veins, but only weakly transcribed in most arteries. To examine whether endothelial cells are committed to an arterial or venous fate once they express these specific receptors, we constructed quail-chick chimeras. The dorsal aorta, carotid artery and the cardinal and jugular veins were isolated together with the vessel wall from quail embryos between embryonic day 2 to 15 and grafted into the coelom of chick hosts. Until embryonic day 7, all grafts yielded endothelial cells that colonized both host arteries and veins. After embryonic day 7, endothelial plasticity was progressively lost and from embryonic day 11 grafts of arteries yielded endothelial cells that colonized only chick arteries and rarely reached the host veins, while grafts of jugular veins colonized mainly host veins. When isolated from the vessel wall, quail aortic endothelial cells from embryonic day 11 embryos were able to colonize both host arteries and veins. Our results show that despite the expression of arterial or venous markers the endothelium remains plastic with regard to arterial-venous differentiation until late in embryonic development and point to a role for the vessel wall in endothelial plasticity and vessel identity.     

No effect of brain blood flow on ventilatory depression during sustained hypoxia

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10-25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9-21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of respiratory center output in the unanesthetized fetal sheep "in utero".

Diaphragmatic electromyographic activity, tracheal and amniotic fluid pressures, lung liquid flow, and carotid and jugular venous pressures were measured on eight fetal lambs who survived for periods of 9-43 days postoperatively. The fetal gestational age ranged from 98 to 113 days at operation. Respiratory center output of the fetus as indicated by electromyographic activity was modified by the following stimuli. It was suppressed by anesthesia and fetal hypoxia (Pao2 = 12 mmHg), tonically reduced by lung inflation, and stimulated by cyanide injections (150-600 mug) into the fetal jugular vein. Neuromuscular transmission to the diaphragm was blocked with d-tubocurarine (0.2-0.6 mg). These experiments indicate that central and motor pathways to the diaphragm are sufficiently mature by 101 days in the fetal sheep to permit their output to be modified by chemical and mechanical stimuli.     

The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment

The degree of variability in the temperature difference between the brain and carotid arterial blood is greater than expected from the presumed tight coupling between brain heat production and brain blood flow. In animals with a carotid rete, some of that variability arises in the rete. Using thermometric data loggers in five sheep, we have measured the temperature of arterial blood before it enters the carotid rete and after it has perfused the carotid rete, as well as hypothalamic temperature, every 2 min for between 6 and 12 days. The sheep were conscious, unrestrained, and maintained at an ambient temperature of 20-22 degrees C. On average, carotid arterial blood and brain temperatures were the same, with a decrease in blood temperature of 0.35 degrees C across the rete and then an increase in temperature of the same magnitude between blood leaving the rete and the brain. Rete cooling of arterial blood took place at temperatures below the threshold for selective brain cooling. All of the variability in the temperature difference between carotid artery and brain was attributable statistically to variability in the temperature difference across the rete. The temperature difference between arterial blood leaving the rete and the brain varied from -0.1 to 0.9 degrees C. Some of this variability was related to a thermal inertia of the brain, but the majority we attribute to instability in the relationship between brain blood flow and brain heat production.     

Site specific inelasticity of arterial tissue

Understanding the mechanical behaviour of arterial tissue is vital to the development and analysis of medical devices targeting diseased vessels. During angioplasty and stenting, stress softening and permanent deformation of the vessel wall occur during implantation of the device, however little data exists on the inelastic behaviour of cardiovascular tissue and how this varies through the arterial tree. The aim of this study was to characterise the magnitude of stress softening and inelastic deformations due to loading throughout the arterial tree and to investigate the anisotropic inelastic behaviour of the tissue. Cyclic compression tests were used to investigate the differences in inelastic behaviour for carotid, aorta, femoral and coronary arteries harvested from 3-4 month old female pigs, while the anisotropic behaviour of aortic and carotid tissue was determined using cyclic tensile tests in the longitudinal and circumferential directions. The differences in inelastic behaviour were correlated to the ratio of collagen to elastin content of the arteries. It was found that larger inelastic deformations occurred in muscular arteries (coronary), which had a higher collagen to elastin ratio than elastic arteries (aorta), where the smallest inelastic deformations were observed. Lower magnitude inelastic deformations were observed in the circumferential tensile direction than in the longitudinal tensile direction or due to radial compression. This may be as a result of non-collagenous components in the artery becoming more easily damaged than the collagen fibres during loading. Stress softening was also found to be dependent on artery type. In the future, computational models should consider such site dependant, anisotropic inelastic behaviour in order to better predict the outcomes of interventional procedures such as angioplasty and stenting.     

Temporal relationship between changes in oxytocin and prostaglandin F levels in response to vaginal distension in the pregnant and puerperal ewe.

To investigate the r?le of oxytocin in the increase in utero-ovarian venous prostaglandin F (PGF) level caused by vaginal distension, jugular venous oxytocin and utero-ovarian venous PGF were measured simultaneously in one sheep in late pregnancy and in one sheep shortly before parturition. Vaginal distension raised oxytocin and PGF levels in both animals and oxytocin levels increased before those of PGF. These findings support the suggestion that the elevated PGF levels resulting from vaginal distension are caused by the reflex secretion of oxytocin.     

Structural evidence for insertion of collagen fibres to smooth muscle cells in the carotid arterial system of the giraffe (Giraffa camelopardalis)

Summary Previous anatomical studies have failed to resolve the question relating to whether or not collagen fibres, like elastic fibres, are attached to smooth muscle cells in the arterial wall. The current ultrastructural study demonstrates the insertion of collagen fibres to the sarcolemmal dark areas in the smooth muscle cells of the carotid arterial system of the giraffe. It is concluded, therefore, that this morphological linkage between collagen and smooth muscle cells may facilitate transmission of the force of contraction between the cells and to the surrounding connective tissue framework since the myofilaments appear to be spatially placed in series with the extracellular collagen fibres at the sarcolemmal dark areas.Presented as part of Ph.D. thesis to the University of Nairobi     

Time-course of venous wall biomechanical adaptation in pressure and flow-overload: Assessment by a microstructure-based material model

Arteriovenous fistulae have been previously created by our group, through implantation of e-PTFE grafts between the carotid artery and jugular vein in healthy pigs, to gather comprehensive data on the time-course of the adapted geometry, composition, and biomechanical properties of the venous wall exposed to chronic increases in pressure and flow. The aim of this study was to mathematically assess the biomechanical adaptation of venous wall, by characterizing our previous in vitro inflation/extension testing data obtained 2, 4, and 12 weeks post-fistula, using a microstructure-based material model. Our choice for such a model considered a quadratic function for elastin with a four-fiber family term for collagen, and permitted realistic data characterization for both overloaded and control veins. As structural validation to the hemodynamically-driven differences in the material response, computerized histology was employed to quantitate the composition and orientation of collagen and elastin-fiber networks. The parameter values optimized showed marked differences among the overloaded and control veins, namely decrease in the quadratic function parameters and increase in the four-fiber family parameters. Differences among the two vein types were highlighted with respect to the underlying microstructure, namely the reduced elastin and increased collagen contents induced by pressure and flow-overload. Explicit correlations were found of the material parameters with the two basic scleroprotein contents, substantiating the material model used and the characterization findings presented. Our results are expected to improve the current understanding of the dynamics of venous adaptation under sustained pressure- and flow-overload conditions, for which data are largely unavailable and contradictory.     

Alloxan-induced diabetes mellitus in pregnant sheep and chronic fetal catheterization

25 female sheep of the Texel breed were made hyperglycaemic by administration of alloxan monohydrate (ALX) in early pregnancy and 15 ewes served as controls. Average venous glucose levels (mean +/- standard deviation) increased from 3.5 +/- 0.2 to 14.0 +/- 1.8 mmol/l. All hyperglycaemic sheep were treated with long-acting insulin in doses adjusted individually (0.2-1.0 U/kg per day) to keep glucose levels above 8 mmol/l. After a temporary significant increase, maternal venous concentrations of urea and creatinine returned to normal levels. One sheep died on day 6 after administration of ALX. Another hyperglycaemic sheep died at induction of anaesthesia. Eight hyperglycaemic ewes aborted between days 90 and 128 of gestation. Between days 103 and 135 of gestation the remaining hyperglycaemic (n = 15) and control (n = 15) ewes were operated upon and the fetuses were provided with EEG, nuchal EMG and ECG electrodes and catheters in the trachea, amniotic fluid, jugular vein and carotid artery. Use of the chronic sheep preparation for the study of diabetes mellitus and fetal reactions was successful in 10 out of 25 cases, as in the diabetic group postoperative intra-uterine fetal survival varied between 2 and 19 days and in 10 cases was at least 5 days. Postoperative intrauterine fetal survival in the controls was significantly longer and varied between 4 and 28 days, and in 13 cases was at least 5 days. A highly significant correlation (P less than 10-6) between maternal and fetal blood glucose levels was seen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose uptake and lactate production by the autotransplanted ovary of the ewe during the luteal and follicular phases of the oestrous cycle

Two experiments were carried out on ewes with ovarian autotransplants to estimate the ovarian uptake of glucose and production of lactate. The first was carried out in the luteal phase of the oestrous cycle. Samples of carotid arterial, ovarian venous and jugular venous blood were collected simultaneously for glucose analysis. The arterial concentration of glucose (58.0 ± 5.0 mg/dL; Mean ± SEM) was significantly higher than the ovarian venous concentration (42.3 ± 2.4 mg/dL; P < 0.001). Next, a second more complete experiment was carried out in the luteal and follicular phases of the oestrous cycle. The oestrous cycle was synchronised and samples of carotid arterial, ovarian venous and jugular venous blood were collected simultaneously for glucose and lactate analysis. There were significant positive arterio-venous differences in the concentration of glucose in the luteal (5.6 ± 1.2 mg/dL, mean ± SEM; P = 0.001), early (3.1 ± 0.82 mg/d; P = 0.003) and late follicular (6.4 ± 1.3 mg/dL; P = 0.001) phases of the oestrous cycle. There was a significant negative arterio-ovarian venous difference in the concentration of lactate in only the luteal phase (-2.2 ± 0.96 mg/dL; P = 0.043).The results show significant removal of glucose from the arterial circulation during its passage through the ovary in the luteal, early follicular and late follicular phases of the oestrous cycle. Furthermore, there was lactate production in the luteal phase but not in the follicular phase suggesting that in the luteal phase of the oestrous cycle, ovarian metabolism can be anaerobic.     

Biaxial mechanical properties of bovine jugular venous valve leaflet tissues

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress–strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress–strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson’s trichrome and Verhoeff–Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic; \(p<0.01\)); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors’ knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.     

Regional transcranial oximetry with near infrared spectroscopy (NIRS) in comparison with measuring oxygen saturation in the jugular bulb in infants and children for monitoring cerebral oxygenation]

Using a dual channel near infrared (NIR) in vivo optical spectroscopy (INVOS) system (INVOS 3100A, Somanetics Corp. Troy, MI, USA) we investigated the relationship between jugular venous oxygen saturation (SjvO2) and regional cerebral oxygen saturation (rSO2) in 30 infants and children (mean age 4.5 years) with congenital heart disease undergoing cardiac catheterisation. The NIRS-SomaSensor (emitter and dual receiver probe) was applied at a standardised right fronto-temporal location (over the right frontal cortex) on the infant's head and covered with an adhesive flexible bandage. Using NIR light (730 and 810 nm) and two source-detector spacings (3 and 4 cm from the transmitter), percentage values of rSO2 were calculated from detected haemoglobin saturations. Simultaneously, jugular venous oxygen saturation (SjvO2) monitoring was performed via a catheter placed in the right internal jugular vein with its tip positioned in the jugular bulb, as verified by fluoroscopy. To compare the reliability of NIRS measurement characteristics, jugular venous blood was analysed for SjvO2 as a reference measure of global cerebral oxygenation, by co-oximetry (OSM3-Hemoximeter, Radiometer Copenhagen, Denmark). Other measured variables included pulse oximetry, arterial blood pressure, and venous and arterial oxygen saturations. Over a jugular venous oxygen saturation range of 31-83%, a significant positive linear correlation was found between rSO2 (NIRS measurement) and SjvO2 (jugular bulb oximetry) (r = 0.93, p < 0.001). No significant correlation was observed between rSO2 values and arterial blood saturation or pulse oximetry. The quantitative correlation between rSO2 (haemoglobin oxygenation in a small hemi-elliptical area of the brain) and reference SjvO2 measurement (method for monitoring global cerebral oxygenation) suggests that NIRS measurement with subtraction algorithm should identify predominantly intracranial saturation in the pediatric age group, and will tend to reflect global oxygenation under physiological conditions. Transcranial oximetry using dual receiving channel NIRS offers a noninvasive, real-time, reliable and practicable means of monitoring cerebral haemoglobin oxygenation changes infants and children with cyanotic and noncyanotic congenital heart disease.     

Anatomy and Histology of the Cephalic Arterial Coilings in Hammerhead Sharks (Genus Sphyrna)

Hammerhead sharks (genus Sphyrna) show two large arterial coilings in a posteroventral hollow of the orbitary cavity. The posterior is made up of the hyoid artery which, after giving rise to the stapedial artery, enters the chondrocranium to originate the internal carotid and the cerebral arteries. The efferent pseudobranchial artery forms the anterior coiling, gives rise to the ophthalmic artery, enters the orbitary wall and joins the internal carotid artery. The histological sections of the arterial coilings showed the scarcity of smooth muscle cells in the tunica media as well as an important collagenic and elastic component in the arterial wall. Several venous vessels percolate through the coilings. A large amount of small (mean diameter = 73 μm), spheric corpuscles were observed in the connective tissue around the coilings. These corpuscles were also present in the palate and under the skin of the head of these sharks. They are comprised of spirally-arranged cells around a bundle of collagen fibres. We hypothesize that their association with the coilings could suggest some kind of involvement in detecting pressure changes in the blood supply to the head.