Fast and Effective Nonsuture Anastomosis of Magnetic Artificial Blood Vessel Transplantation for Caval Reconstruction in Canines.

BACKGROUND: The resection and reconstruction of the vena cava is frequently needed in tumor resection. The goal of this study was to evaluate the performance of the magnetic compression anastomosis (MCA) device for fast nonsuture anastomosis of caval reconstruction with artificial blood vessel transplantation after resection in canines. METHODS: The MCA device consisted of paired neodymium-ferrum-boron (Nd-Fe-B) magnetic rings that were coated with titanium nitride and embedded in a polypropylene shell. Artificial blood vessel transplantation procedure was performed in sixteen canines and then they were divided into 2 groups: MCA group (n = 8), in which the novel magnetic pinned-ring device was used, and the traditional manual suture group (n = 8). In situ artificial blood vessel anastomoses were performed in the inferior vena cava (IVC). The anastomosis time and anastomotic patency and quality were investigated through ultrasonographic scans, angiographic, gross observation, histological staining, and scanning electron microscopy at 24 weeks postoperatively. RESULTS: The IVC anastomoses were reconstructed successfully in all canines and all animals survived. In the MCA group, the operation time for IVC anastomosis with artificial blood vessel was significantly shorter than that in the tradition manual suture group (P < 0.05). Vena cava angiography and ultrasound showed good blood patency. The scanning electron microscope showed the re-endothelialization was smooth and endothelial cells were arranged regularly at the anastomotic site. Histological examination confirmed that the MCA group was associated with infiltration of inflammatory cells compared with the manual suture group. CONCLUSIONS: The MCA device combined with artificial blood vessels is applicable in reconstruction of large vessels after resection. The magnetic pinned-ring device offers a simple, fast, reliable, and effective technique for nonsuture artificial blood vessel anastomosis of caval reconstruction in canines, and the anastomosis is functionally better than the traditional sutured anastomosis.

Study on the Patency of the Contralateral Iliac Vein After Stenting Across the Iliocaval Confluence With an Experimental In Vivo Model.

OBJECTIVE: Stenting is the preferred treatment for iliac vein lesions. For the treatment of occlusions in the junction of the iliac vein and the inferior vena cava (IVC), the stent needs to be positioned in the IVC to cover the lesion. However, the pathological changes in the contralateral iliac vein due to stent coverage on its ostium remain unclear. We observed the patency of the contralateral iliac vein via animal experiments. METHODS: The stents were placed in the left iliac vein and extended into the IVC in 8 beagle dogs. Doppler ultrasonography, angiography, and histopathological examination were used to assess the patency and histopathological changes in the contralateral iliac vein. RESULTS: Angiography showed patency of the contralateral iliac vein and no sign of thrombosis or stenosis. Twelve months after stenting, Doppler ultrasonography showed a stenotic change in the ostium of the contralateral iliac vein. The histopathological examination showed that the stent strut at the ostium of the contralateral iliac vein was mostly covered by the intima, and the cross-sectional stenosis rate was greater than 60%. CONCLUSIONS: The coverage of the iliac vein stent on the ostium of the contralateral iliac vein does not cause complete occlusion of the contralateral vein but can cause significant stenosis at the ostium of the contralateral iliac vein, which is considered to be a potential risk factor for thrombosis.

Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus: A Multi-institutional Analysis from the International Renal Cell Carcinoma-Venous Thrombus Consortium.

BACKGROUND: Microscopic vein invasion (MVI), with local destruction and invasion of the endothelium by tumor, is of controversial predictive value in renal cell carcinoma (RCC). OBJECTIVE: To assess the impact of venous extension and wall invasion in RCC on survival. DESIGN, SETTING, AND PARTICIPANTS: Data for 1023 RCC patients with vena cava thrombus treated with radical nephrectomy and complete tumor thrombectomy were collected within a prospectively maintained international consortium (1995-2012). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Kaplan-Meier method and univariable and multivariable Cox regression analyses were used to assess the impact of MVI on cancer-specific survival (CSS). The main two variables of interest were microscopic renal vein wall invasion (MRVI) and microscopic vena cava wall invasion (MVCI). RESULTS: MRVI was found in 725 cases (70.9%) and MVCI in 230 (22.5%). Patients with MRVI had larger tumors (p=0.005), longer hospital stay (p<0.001), higher clinical stage 0.039), higher Fuhrman grade (p=0.028), and more frequent fat invasion. Presence of MVCI was associated with larger tumors (p<0.001), longer hospital stay (p<0.001), higher clinical stage (p<0.001), lymph node involvement (p=0.045), higher Fuhrman grade (p<0.001), and higher thrombus level (p<0.001). With median follow-up of 52 mo, overall 5-yr CSS was 57.4%. Multivariable analysis showed that presence of MRVI was an independent factor related to CSS (hazard ratio 2.24, 95% confidence interval 1.24-3.59, p=0.006). The main limitation was the inability to report MVI percentages. CONCLUSIONS: Patients with MRVI experience significantly worse survival outcomes after radical nephrectomy and tumor thrombectomy. Consideration of MRVI at final pathology is appropriate to improve decision-making for risk-adapted follow-up. PATIENT SUMMARY: The behavior of locally advanced renal cell carcinoma (RCC) depends on clinical and pathologic factors. Analysis revealed that RCC patients with microscopic renal vein wall invasion experience significantly worse cancer-specific survival.

Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway.

Exogenous administration of melatonin has been demonstrated to down-regulate inflammatory responses and attenuate organ damage in various models. However, the salutary effect of melatonin against secondary intra-abdominal hypertension (IAH) remains unclear. This study sought to test the influence of melatonin on secondary IAH in a pathophysiological rat model and the underlying mechanisms involved. Before resuscitation, male rats underwent a combination of induced portal hypertension, applying an abdominal restraint device, and hemorrhaging to mean arterial pressure (MAP) of 40mmHg for 2h. After blood reinfusion, the rats were treated with lactated Ringer solution (LR) (30mL/h), melatonin (50mg/kg) +LR, and SB-203580 (10µmol/kg)+LR. LR was continuously infused for 6h. MAP, the inferior vena cava pressure and urine output were monitored. Histopathological examination, immunofluorescence of tight junction proteins, and transmission electron microscopy were administered. Intestinal permeability, myeloperoxidase activity, malondialdehyde, glutathione peroxidase, and levels of TNF-a, IL-2, and IL-6, were assessed. The expression of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, translocation of nuclear factor kappa B subunit, signal transducers and activators of transcription and tight junction proteins were detected by Western blot. We found that melatonin inhibited the inflammatory responses, decreased expression of p38 MAPK, attenuated intestinal injury, and prevented secondary IAH. Moreover, administration of SB203580 abolished the increase in p38 MAPK and also attenuated intestinal injury. These data indicate that melatonin exerts a protective effect in intestine in secondary IAH primarily by attenuating the inflammatory responses which are in part attributable to p38 MAPK inhibition.

Decreased Intrathoracic Impedance Associated With OptiVol Alert Can Diagnose Increased B-Type Natriuretic Peptide - MOMOTARO (Monitoring and Management of OptiVol Alert to Reduce Heart Failure Hospitalization) Study - .

BACKGROUND: Ambulatory measurement of intrathoracic impedance (ITI) with an implanted device may detect increases in pulmonary fluid retention early, but the clinical utility of this method is not well established. The goal of this study was to test whether conventional ITI-derived parameters can diagnose fluid retention that may cause early stage heart failure (HF). METHODS AND RESULTS: HF patients implanted with high-energy devices with OptiVol (Medtronic) monitoring were enrolled in this study. Patients were monitored remotely. At both baseline and OptiVol alert, patients were assessed on standard examinations, including analysis of serum brain natriuretic peptide (BNP). From April 2010 to August 2011, 195 patients from 12 institutes were enrolled. There were 154 primary OptiVol alert events. BNP level at the alerts was not significantly different from that at baseline. Given that ITI was inversely correlated with log BNP, we added a criterion specifying that the OptiVol alert is triggered only when ITI decreases by ≥4% from baseline. This change improved the diagnostic potential of increase in BNP at OptiVol alert (sensitivity, 75%; specificity, 88%). CONCLUSIONS: BNP increase could not be identified based on OptiVol alert. Decrease in ITI ≥4% compared with baseline, in addition to the alert, however, may be a useful marker for the likelihood of HF (Clinical trial info: UMIN000003351).

[Computerized three-dimensional reconstruction of the retrohepatic segment of inferior vena cava of a 20 mm human embryo]. / Reconstruction tridimensionnelle informatisée du segment rétrohépatique de la veine cave inférieure d'un embryon humain de 20mm.

The subdiaphragmatic venous drainage of the embryo is provided by the two caudal cardinal veins to which is added the subcardinal vein system, draining the mesonephros, the perispinal supracardinal veins and the umbilical and vitelline venous system. The anastomosis of certain segments of the embryonic venous structures and the disappearance of others are at the origin of the inferior vena cava. Since the 19th century, three-dimensional reconstruction of solid models from histological sections were developed. At present, the development of computerized three-dimensional reconstruction techniques allowed to operate a multitude of techniques of image processing and modeling in space. Three-dimensional reconstruction is a tool for teaching and research very useful in embryological studies because of the obvious difficulty of dissection and the necessity of introducing time as the fourth dimension in the study of organogenesis. This method represents a promising alternative compared to previous three-dimensional reconstruction techniques including Born technique. The aim of our work was to create a three-dimensional computer reconstruction of the retrohepatic segment of the inferior vena cava of a 20mm embryo from the embryo collection of Saints-Pères institute of anatomy (Paris Descartes university, Paris, France) to specify the path relative to the liver and initiate a series of computerized three-dimensional reconstruction that will follow the evolution of this segment of the inferior vena cava and this in a pedagogical and morphological research introducing the time as the fourth dimension.

Nonsuture anastomosis of arteries and veins using the magnetic pinned-ring device: a histologic and scanning electron microscopic study.

BACKGROUND: The goal of this study was to evaluate the performance of the magnetic pinned-ring device for nonsuture vascular anastomosis. METHODS: The magnetic pinned-ring device consists of paired magnetic rings that are coated with titanium nitride and embedded in a polypropylene shell; the rings are equipped with alternately spaced holes and titanium pins. The vascular anastomosis procedure using the novel magnetic pinned-ring device was performed on 14 mongrel dogs, and the traditional hand-sewing technique was used on 14 additional dogs. In situ end-to-end anastomoses were performed in the femoral artery and the inferior vena cava. Patency was confirmed through ultrasonographic scans at different time points as late as 24 weeks after surgery. Gross observation, histological staining, and scanning electron microscopy were used to evaluate the results at 24 weeks postoperatively. RESULTS: The time required to perform the vascular anastomosis was significantly shorter for the magnetic device than for hand sewing. A continuity of re-endothelialization was confirmed in all anastomotic stomas after 24 weeks, and neither formation of aneurysms nor thickening of the vascular wall was noted. The re-endothelialization was smooth at the anastomotic site of the magnetic device, whereas hand sewing resulted in rough and uneven re-endothelialization and the presence of visible sutures. Moreover, the endothelial cells were regularly arranged at the anastomotic site of the magnetic device, whereas different-sized and irregularly aligned endothelial cells were present at the hand-sewn anastomotic site. Use of the magnetic device was associated with significantly decreased deposition of fibrotic collagen and depressed infiltration of inflammatory cells compared with use of the hand-sewing technique. CONCLUSIONS: The magnetic pinned-ring device offers a simple, fast, reliable, and efficacious technique for nonsuture vascular anastomosis. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of vascular tissue.

Leiomiosarcoma de la vena cava inferior. Presentación de un caso y revisión del cuadro clinicopatológico / Leiomyosarcoma of the inferior vena cava. A case report and review of the clinical and pathological features

Se presenta el caso de un hombre de 63 años de edad con leiomiosarcoma de la vena cava inferior que falleció por síndrome de vena cava inferior secundario al tumor. Se realizó el estudio de autopsia donde se demuestra el sitio primario de la neoplasia, así como reacciones de inmunohistoquímica para confirmar su estirpe histológica. Se hace una revisión de la literatura, ilustrando las características morfológicas, y se discuten los diagnósticos diferenciales(AU)

We present a case of leiomyosarcoma of the inferior vena cava in a 63 year old man who subsequently died due to vena cava syndrome secondary to the tumour. Autopsy revealed the primary neoplasm, and immunohistochemistry confirmed the histological diagnosis. Morphology and differential diagnosis are discussed together with a review of the literature(AU)

Antithrombotic effect of grape seed proanthocyanidins extract in a rat model of deep vein thrombosis.

OBJECTIVE: Proanthocyanidins are abundantly found in grape seeds and have been suggested to inhibit the pathogenesis of systemic diseases. We investigated the antithrombotic effects of proanthocyanidins in a rat model of deep vein thrombosis (DVT) and examined the underlying mechanisms. METHODS: DVT was induced in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to the experimental rats. Control rats were administrated saline (2 mL) only. The thrombi were harvested and weighed. The IVC was analyzed histologically and by transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi was examined by Western blot. RESULTS: GSPE significantly reduced thrombus length and weight (P < .01) and protected the integrity of the endothelium. GSPE inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13). Compared with the control, GSPE significantly lowered the cytokines IL-6 (74.19 ± 13.86 vs 189.54 ± 43.76 pg/mL; P < .01), IL-8 (80.71 ± 21.42 vs 164.56 ± 39.54 pg/mL; P < .01), and TNF-α (43.11 ± 17.58 vs 231.84 ± 84.11 pg/mL; P < .01). CONCLUSIONS: GSPE significantly inhibited the propagation of thrombus induced by IVC ligation in a rat model. The antithrombotic properties of proanthocyanidins are likely to be directly associated with endothelial protection and regeneration, platelet aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus, proanthocyanidins may have a clinical application in DVT treatment.

Thrombogenesis with continuous blood flow in the inferior vena cava. A novel mouse model.

Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (DCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 muAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 muAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in DCT vs. WT (WT/PAI-1: p=0.003, WT/DCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow.

Regional histomorphometry of the hepatic inferior vena cava; a possible sphincteric mechanism / Histomorfometría regional de la vena cava inferior hepática; un posible mecanismo de esfínter

This study was aimed at identifying the changes in diameter and structural composition of the Hepatic Inferior Vena Cava in its infrahepatic, intrahepatic and suprahepatic portions. Eighty adult liver specimens from the Chiromo and Nairobi City mortuaries were used for morphometry, while twenty of them were processed for light microscopy. A constriction was noted in the mid-portion of the HIVC, while structurally; the intrahepatic portion had thicker fibromuscular adventitia. It is plausible that these are sphincteric apparatus to prevent backflow of blood in the Hepatic Inferior Vena Cava.

Este estudio tiene por objetivo identificar los cambios en el diámetro y la composición estructural de la vena cava inferior hepática en sus porciones infrahepática, intrahepática y suprahepática. Ochenta hígados de especímenes adultos de los depósitos de cadáveres de la ciudad de Nairobi y Chiromo fueron usadas para morfometría, mientras que veinte de ellos fueron procesados para microscopía de luz. Se observó una constricción en el medio de la HIVC, mientras que estructuralmente, la porción intrahepática había una gruesa adventicia fibromuscular. Es posible que este sea un aparato esfinteriano para evitar el reflujo de sangre en la vena cava inferior hepática.

Vascular remodeling and its role in the pathogenesis of ascites in fast growing commercial broilers.

This study examined the putative role of blood vessel pathology in the development of ascites in broilers. Major blood vessels (aorta, brachiocephalic arteries, pulmonary arteries, and vena cava) from normal commercial male broiler chickens, and broilers that developed congestive heart failure (CHF) with or without ascites were subjected to gross and microscopic examination. On cross-section, grossly, the arteries from normal broilers and those showing dilated cardiomyopathy without ascites appeared circular, with firm wall tone characteristic of the normal artery. In contrast, the arteries from ascitic broilers appeared flaccid and lacked elasticity, which was evidenced by collapsing, ellipsoid cross-sectional arterial lumen owing to the structural weakness of the arterial walls. Microscopically, ascitic broilers showed thinning or occasionally total loss of elastic elements in the arterial wall, and reduced network density of the structural matrix of the vascular wall, as well as increased thickness of fibers in vena cava. The structural changes seen in the major arteries from ascitic broilers are maladaptive, and as such would definitively impose an increased hemodynamic burden on the already failing heart pump. The changes in veins are indicative of pathological remodeling conducive to increased permeability of the vascular wall, particularly in the situation when a poorly distensible structure is further subjected to wall stress associated with increased pressure and volume overload. Taken together, increased hemodynamic burden and reduced structural density of the venous wall constitute conditions conducive for seepage and accumulation of ascitic fluid.

[Clinico-diagnostic criteria for application of antiembolic cava-filter at various terms after its implantation].

Cava-filter implantation procedure constitutes an effective method for the pulmonary thromboembolism surgical prophylaxis. After cava-filter implantation completion the ultrasonography, contrast cavagraphy and spiral computer tomography (CT) were performed of the vena cava inferior (IVC) portion in the site of embolcatching device installation. The cava-filters models investigated, owing the cone form without flattening part, make a jump while exiling from the delivery system and occupy angulation position in IVC lumen. The IVC wall perforation after the operation had occurred in 3 (1.6%) patients, in far remote period the neighboring organs wall perforation was observed in 17 (85%) patients. In late follow-up period the complete or partial IVC occlusion was noted at the site of the embolcatching devices residence with chronic venous insufficiency occurrence. Subsequent complex studying and essential improvement of antithrombotic cava-filters is needed for prevention of the filters application complications.

Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder associated with ciliary defects and situs inversus totalis, the complete mirror image reversal of internal organ situs (positioning). A variable incidence of heterotaxy, or irregular organ situs, also has been reported in PCD patients, but it is not known whether this is elicited by the PCD-causing genetic lesion. We studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene commonly mutated in PCD. Analysis of homozygous mutant embryos from 18 litters yielded 25% with normal organ situs, 35% with situs inversus totalis, and 40% with heterotaxy. Embryos with heterotaxy had complex structural heart defects that included discordant atrioventricular and ventricular outflow situs and atrial/pulmonary isomerisms. Variable combinations of a distinct set of cardiovascular anomalies were observed, including superior-inferior ventricles, great artery alignment defects, and interrupted inferior vena cava with azygos continuation. The surprisingly high incidence of heterotaxy led us to evaluate the diagnosis of PCD. PCD was confirmed by EM, which revealed missing outer dynein arms in the respiratory cilia. Ciliary dyskinesia was observed by videomicroscopy. These findings show that Dnahc5 is required for the specification of left-right asymmetry and suggest that the PCD-causing Dnahc5 mutation may also be associated with heterotaxy.

Transport in rat vessel walls. II. Macromolecular leakage and focal spot size growth in rat arteries and veins.

Transendothelial lipid transport into and spread in the subendothelial intima of large arteries, and subsequent lipid accumulation, appear to start plaque formation. We experimentally examine transendothelial horseradish peroxidase (HRP) transport in vessels that are usually, e.g., pulmonary artery (PA), or almost always, e.g., inferior vena cava (IVC), atherosclerosis resistant vs. disease prone, e.g., aorta, vessels. In these vessels, HRP traverses the endothelium at isolated, focal spots, rather than uniformly, for short circulation times. For femoral vein HRP introduction, PA spots have 30-s radii [ approximately 53.2 microm (SD 10.4); compare aorta: 54.6 microm (SD 8.75)] and grow quickly from 30 s to 1 min (40%, P<0.05) and more slowly afterward (P>0.05). This trend resembles the aorta, suggesting the PA has a similarly sparse intima. With carotid artery (CA) HRP introduction, the 30-s spot (132.86 +/- 37.32 microm) is far larger than the PAs, grows little ( approximately 28%, P<0.05) from 30 to 60 s, and is much flatter than the artery curves. Transverse electron microscopic sections after approximately 10 min HRP circulation show thin, intense staining immediately beneath both vessels' endothelia with an almost step change to diffuse staining beyond. This indicates the existence of a sparse, subendothelial intima, even when there is no internal elastic lamina (IVC). This motivates a simple model that translates growth rates into lower bounds for the flow through focal leaks. The model results and our earlier wall and medial hydraulic conductivity data explain these spot growth curves and point to differences in transport patterns that might be relevant in understanding the immunity of IVC to disease initiation.

The inferior right atrial isthmus: further architectural insights for current and coming ablation technologies.

BACKGROUND: Although linear ablation of the right atrial isthmus in patients with isthmus-dependent atrial flutter can be highly successful, recurrences and complications occur in some patients. Our study provides further morphological details for a better understanding of the structure of the isthmus. METHODS AND RESULTS: We examined the isthmic area in 30 heart specimens by dissection, histology, and scanning electron microscopy. This area was bordered anteriorly by the hinge of the tricuspid valve and posteriorly by the orifice of the inferior caval vein. With the heart in attitudinal orientation, we identified and measured the lengths of three levels of isthmus: paraseptal (24 +/- 4 mm), central (19 +/- 4 mm), and inferolateral (30 +/- 3 mm). Comparing the three levels, the central isthmus had the thinnest muscular wall and the paraseptal isthmus the thickest wall. At all three levels, the anterior part was consistently muscular whereas the posterior part was composed of mainly fibro-fatty tissue in 63% of hearts. The right coronary artery was less than 4 mm from the endocardial surface of the inferolateral isthmus in 47% of hearts. Inferior extensions of the atrioventricular node were present in the paraseptal isthmus in 10% of hearts, at 1-3 mm from the endocardial surface. CONCLUSIONS: The thinner wall and shorter length of the central isthmus together with its distance from the right coronary artery, and nonassociation with the atrioventricular node or its arterial supply, should make it the preferred site for linear radiofrequency ablation.

Calyculin-A disrupts subplasmalemmal junction and recurring Ca2+ waves in vascular smooth muscle.

Excitation-contraction coupling (E-C coupling) in phenylephrine(PE)-stimulated rabbit inferior vena cava (IVC) depends on the generation of asynchronous recurring Ca2+ waves in the in situ vascular smooth muscle cells (VSMC). Previous studies by our group have implicated a putative non-selective cationic store-operated channel and the reverse-mode Na+-Ca2+ exchange in refilling of the intracellular Ca2+ store via the sarco/endoplasmic reticulum ATPase (SERCA) and the maintenance of the recurring Ca2+ waves. We hypothesize that for the proper functioning of these three Ca2+ translocators in the process of SR refilling, the plasma membrane (PM) and the underlying superficial sarcoplasmic reticulum (SR) form specialized PM-SR junctions, which are essential for the maintenance of the recurring Ca2+ waves. In order to test this hypothesis, calyculin-A, a serine/threonine phosphatase inhibitor that has been demonstrated to result in the disruption of the PM-SR junctions was used. In the control rabbit IVC, electron microscopy of the in situ VSMC indicates that 14.2+/-0.7% of the PM is closely apposed by the prominent superficial SR network, forming numerous flattened PM-SR junctional cytoplasmic spaces. In the control IVC stimulation with 5 microM PE resulted in sustained recurring Ca2+ waves with a frequency of 0.42+/-0.02 Hz. In calyculin-A treated rabbit IVC, a concentration-dependent dissociation of the superficial SR and loss of PM-SR junctions was observed. This progressive loss of the PM-SR junctions occurs over the same concentration range as the inhibition of PE-induced recurring Ca2+ waves. These findings offer support for the hypothesis that the presence of the PM-SR junctions is required for the generation of asynchronous recurring Ca2+ waves, which underlie excitation-contraction coupling in the VSMC of the rabbit IVC.

Endothelin-induced constriction of the ductus venosus in fetal sheep: developmental aspects and possible interaction with vasodilatory prostaglandin.

1. The ductus venosus is actively regulated in the fetus, but questions remain on the presence of a functional sphincter at its inlet. Using fetal sheep (0.6-0.7 gestation onwards), we have examined the morphology of the vessel and have also determined whether endothelin-1 (ET-1) qualifies as a natural constrictor being modulated by prostaglandins (PGs). 2. Masson's staining and alpha-actin immunohistochemistry showed a muscular, sphincter-like formation at the ductus inlet and a muscle layer within the wall of the vessel proper. This muscle cell component increased with age. 3. ET-1 contracted dose-dependently isolated sphincter and extrasphincter preparations of the ductus from term fetus. This ET-1 effect also occurred in the premature, but its threshold was higher. 4. BQ123 (1 microm) caused a rightward shift in the ET-1 dose-response curve, while indomethacin at a threshold concentration (28 nm) tended to have an opposite effect. 5. Big ET-1 also contracted the ductus sphincter but differed from ET-1 for its lesser potency and inhibition by phosphoramidon (50 microm). 6. The ductus sphincter (term and preterm) and extrasphincter (term) released 6-keto-PGF(1alpha) (hence PGI(2)) and, to a lesser degree, PGE(2) at rest and their release increased dose-dependently upon ET-1 treatment. Both basal and stimulated release was curtailed by endothelium removal. 7. BQ123 and phosphoramidon reduced slightly the contraction of ductus sphincter to indomethacin (2.8 microm). 8. We conclude that the ductus contains a contractile mechanism in the sphincter and extrasphincter regions. ET-1 lends itself to a role in the generation of contractile tone and its action may be modulated by prostaglandins.

Development of the ductus venosus in the SD rat.

We used scanning electron microscopy to observe the development of the ductus venosus in the fetal rat liver. At day 13 of gestation, the vascular system in the liver was already formed and the umbilical vein had branched many capillaries to the parenchyma of the liver and was connected to the posterior vena cava directly by one small ductus venosus. At day 14 of gestation, the umbilical vein bulged at its terminal part and bifurcated into the ductus venosus, which joined the posterior vena cava, and a branch that anastomosed with the vitelline vein. The ductus venosus had no branches and subsequently enlarged and then degenerated just before birth. The bulging part of the umbilical vein and its branches degenerated in the later stages of gestation. The vitelline vein developed to form the capillaries of the liver and the intestinal venous system. In the SD rat liver, the ductus venosus was therefore established by development of the terminal part of the umbilical vein, which anastomosed directly with the posterior vena cava.