Development of blood access using new materials

Conclusion Thrombosis, narrowing, obstruction, infection, pseudoaneurysm formation, arterial steal syndrome, venous hypertension, and congestive heart failure are common complications in HD patients with primary or autogenous AV fistulas, prosthetic graft AV shunts, or permanent catheters.The most important problem is that we still do not have enough suitable prosthetic graft for the AV shunt. Historically. The AV shunt was developed for use in cardiovascular diseases. The used for frequent puncture and the risk of infection were not anticipated. We hope to develop a suitable prosthetic graft for the AV shunt. Next, the development of interventional radioangioplasty will help HD patients. Last, the no-needle approach, like the external catheter, should be considered more for the treatment of HD patients.     

Formation of new tissue from an arteriovenous loop in the absence of added extracellular matrix

A major requirement for the microsurgical repair of contour defects of the skin, for example, following removal of a skin cancer on the face, is a mass of vascularised subcutaneous tissue. Such tissue can be generated in vivo using basic tissue engineering principles. In previous studies in our laboratory, we have used a model comprising an arteriovenous (AV) shunt loop sandwiched in artificial dermis, placed in a cylindrical plastic growth chamber, and inserted subcutaneously to grow new connective tissue progressively up to 4 weeks. To learn more about the basic growth characteristics with this model, the same AV shunt loop within a chamber without added extracellular matrix was inserted subcutaneously into the groins of rats for 2, 4, or 12 weeks (n = 5 per group). There was a progressive increase in the mass and volume of tissue such that the chamber was two-thirds full after 12 weeks. Histological examination showed that at 2 weeks there was evidence of fibroblast and vascular outgrowth from the AV shunt, with the formation of granulation tissue, surrounded by a mass of coagulated exudate. At 4 weeks the connective tissue deposition was more extensive, with a mass of more mature granulation tissue containing considerable collagen. By 12 weeks there was an extensive, well vascularized mass of mature fibrous tissue. The blood vessels and residual adventitia of the AV shunt were the likely source of growth factors and of the cells which populated the chamber with new maturing connective tissue. A patent AV shunt in an isolated chamber appears to be the minimal requirement for the generation of new vascularized tissue that is potentially suitable for microsurgical transplantation.     

Parylene MEMS patency sensor for assessment of hydrocephalus shunt obstruction

Neurosurgical ventricular shunts inserted to treat hydrocephalus experience a cumulative failure rate of 80 % over 12 years; obstruction is responsible for most failures with a majority occurring at the proximal catheter. Current diagnosis of shunt malfunction is imprecise and involves neuroimaging studies and shunt tapping, an invasive measurement of intracranial pressure and shunt patency. These patients often present emergently and a delay in care has dire consequences. A microelectromechanical systems (MEMS) patency sensor was developed to enable direct and quantitative tracking of shunt patency in order to detect proximal shunt occlusion prior to the development of clinical symptoms thereby avoiding delays in treatment. The sensor was fabricated on a flexible polymer substrate to eventually allow integration into a shunt. In this study, the sensor was packaged for use with external ventricular drainage systems for clinical validation. Insights into the transduction mechanism of the sensor were obtained. The impact of electrode size, clinically relevant temperatures and flows, and hydrogen peroxide (H₂O₂) plasma sterilization on sensor function were evaluated. Sensor performance in the presence of static and dynamic obstruction was demonstrated using 3 different models of obstruction. Electrode size was found to have a minimal effect on sensor performance and increased temperature and flow resulted in a slight decrease in the baseline impedance due to an increase in ionic mobility. However, sensor response did not vary within clinically relevant temperature and flow ranges. H₂O₂ plasma sterilization also had no effect on sensor performance. This low power and simple format sensor was developed with the intention of future integration into shunts for wireless monitoring of shunt state and more importantly, a more accurate and timely diagnosis of shunt failure.     

Prenatal cardiovascular shunts in amniotic vertebrates

During amniotic vertebrate development, the embryo and fetus employ a number of cardiovascular shunts. These shunts provide a right-to-left shunt of blood and are essential components of embryonic life ensuring proper blood circulation to developing organs and fetal gas exchanger, as well as bypassing the pulmonary circuit and the unventilated, fluid filled lungs. In this review we examine and compare the embryonic shunts available for fetal mammals and embryonic reptiles, including lizards, crocodilians, and birds. These groups have either a single ductus arteriosus (mammals) or paired ductus arteriosi that provide a right-to-left shunt of right ventricular output away from the unventilated lungs. The mammalian foramen ovale and the avian atrial foramina function as a right-to-left shunt of blood between the atria. The presence of atrial shunts in non-avian reptiles is unknown. Mammals have a venous shunt, the ductus venosus that diverts umbilical venous return away from the liver and towards the inferior vena cava and foramen ovale. Reptiles do not have a ductus venosus during the latter two thirds of development. While the fetal shunts are well characterized in numerous mammalian species, much less is known about the developmental physiology of the reptilian embryonic shunts. In the last years, the reactivity and the process of closure of the ductus arteriosus have been characterized in the chicken and the emu. In contrast, much less is known about embryonic shunts in the non-avian reptiles. It is possible that the single ventricle found in lizards, snakes, and turtles and the origin of the left aorta in the crocodilians play a significant role in the right-to-left embryonic shunt in these species.     

Prenatal diagnosis and fetal therapy of congenital cystic adenomatoid malformation type I of the lung: a report of five cases

ABSTRACT  We experienced five pregnancy cases with type I congenital cystic adenomatoid malformation (CCAM) of fetuses and summarized here their clinical characteristics, pregnancy outcomes, and fetal therapies. Four of five cases were prenatally diagnosed using magnetic resonance imaging (MRI) as having lung abnormality, and the remaining case was prenatally diagnosed as having congenital diaphragmatic herniation (CDH). One fetus underwent the puncture of cysts in the lung, and two fetuses received in utero thoracoshunts between cysts and the amniotic fluid cavity (thoracoamniotic shunt). One pregnancy ended in artificial termination at 17 gestational weeks, and 4 pregnancies succeeded in live births. All these 4 infants underwent surgical operations for CCAM, and 1 infant underwent an additional operation for CDH. The MRI examinations were useful to prenatally identify CCAM, and the in utero thoracoamniotic shunt appears to be beneficial in preventing lung hypoplasia in the affected fetuses.     

Circulating immune complexes in infected ventriculoatrial and ventriculoperitoneal shunts

Distinguishing infected from noninfected ventriculoatrial (VA) or ventriculoperitoneal (VP) shunts is prognostically and therapeutically important. Eighty-seven serum samples from twenty-seven patients with VA or VP shunts were studied for the presence and quantification of circulating immune complexes. Eighty-three percent of the samples from infected shunts presented circulating immune complexes. Mean values of immune complexes in patients with infected shunts were significantly higher than in those without infection. In febrile, septicemic patients with few clinical symptoms, immune complexes were present, and their measurement in serial serum samples was a significant diagnostic aid. If circulating immune complex levels are not detectable, a shunt infection is less likely to be present.     

Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites

BACKGROUND. There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS. We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS. During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS. The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved.     

Glucocorticosteroid treatment for cerebrospinal fluid eosinophilia in a patient with ventriculoperitonial shunt.

BACKGROUND: Cerebrospinal fluid (CSF) eosinophilia commonly occurs in patients with ventriculoperitoneal (VP) shunts and is associated with shunt complications such as obstruction or infection. Glucocorticosteroids (GCS) are effective in reducing eosinophilia and eosinophils in skin, nasal mucosa, and airway epithelium. Effects of GCS on CSF eosinophils has not been reported. OBJECTIVE: To demonstrate glucocorticosteroid effects on the CSF eosinophil levels and to propose that GCS may be used as a therapeutic agent for CSF eosinophilia. RESULT: A case report of a patient with congenital hydrocephalus and a VP shunt developed CSF eosinophilia associated with latex allergy and shunt malfunction. Daily treatment with 2 mg/kg of methylprednisolone was associated with reduced peripheral eosinophilia and slightly reduced CSF eosinophil counts. Pulse methylprednisolone, 15 mg/kg, was associated with complete reduction of CSF eosinophils and prolonged VP shunt survival. CONCLUSION: Systemic glucocorticosteroids effectively reduce CSF eosinophils. Glucocorticosteroids may be beneficial for treatment of CSF eosinophilia associated with VP shunt malfunction.     

Genesis of renal tubular atrophy in experimental hydronephrosis in the rat. Role of apoptosis

A morphological study was undertaken to assess the role of cell deletion by apoptosis in experimental hydronephrosis. Male Sprague-Dawley rats (200 +/- 20 gm) were used. The left ureter was ligated or a sham operation was carried out. Animals were killed from 4 days to 12 weeks after operation. Two parallel studies were undertaken: one to demonstrate and quantitate specific morphological changes in the affected kidney using light and electron microscopy, and the other to measure changes in dry kidney weights. Renal tubular atrophy is an inevitable consequence of chronic occlusion of the ureter. As expected, the present study showed a progressive loss of tissue mass in the hydronephrotic kidney. This occurred from 1 week after permanent ureteric ligation, and was most rapid between 2 and 4 weeks. The tubular epithelium contained cells undergoing a distinct form of cell death termed apoptosis, characterized ultrastructurally in its early stage by the presence of rounded cells with condensed cytoplasm and condensed and marginated nuclear chromatin, and later by the presence of discrete membrane-bounded intact cellular fragments (apoptotic bodies), which were phagocytosed and digested by adjacent viable cells, or were shed into the tubular lumens. Numbers of apoptotic cells or clusters of apoptotic bodies were increased significantly in all animals with ureteric obstruction in comparison with controls. The greatest increases occurred at 2 and 4 weeks, when loss of renal mass was occurring rapidly. Diminished blood flow in hydronephrosis has been well-documented by others, and therefore our results are consistent with studies which have shown mild ischemia to be the cause of tissue atrophy involving apoptosis. We conclude that cell deletion by apoptosis plays an important role in the pathogenesis of renal tubular atrophy associated with hydronephrosis.     

Flow analysis in vascular shunts that bypass the carotid artery.

When blood flow through a carotid artery is impaired and vascular surgery is necessary to restore adequate circulation a vascular shunt can be applied to maintain cerebral blood flow. Several vascular shunts are commercially available, but there is only limited test data on their flow capacity. The purpose of this study is to determine the flow capacity of three vascular shunt systems. A theoretical model has been developed for this purpose. To validate the model, in vitro flow measurements were taken. Application of the model showed that all shunts cause a decrease in blood flow. The amount of flow decrease varied widely from 13% (Javid shunt) to 55% (Pruitt-Inahara). In vitro measurements confirmed the validity of the model. In conclusion, it is important for the vascular surgeon to realise that vascular shunts show large differences in flow capacity. Of the three investigated shunts, the Javid has the highest flow capacity.     

Evaluation of an aqueous drainage glaucoma device constructed of ePTFE.

Aqueous drainage devices for the treatment of glaucoma are subject to the same limitations as most polymeric implants, namely a healing response comprised of chronic inflammation and fibrosis. The most widely used devices are currently made of silicone or polypropylene, materials that exhibit biocompatibility difficulties when they are implanted on the sclera underneath the conjunctiva of the eye. Decreased outflow of aqueous fluid to the conjunctival space caused by the development of a fibrous capsule around the device accounts for at least 20% of aqueous shunts failures. Clearly, the need exists to improve the healing response to aqueous drainage devices, and one approach is to develop new polymers or polymer modifications. Improved devices would elicit a limited fibrotic response while increasing neovascularization around the implant. Previous studies have indicated that denucleation markedly improves the healing characteristics and biocompatibility of expanded polytetrafluoroethylene (ePTFE). We reasoned that altering the design of drainage devices to allow the use of denucleated ePTFE in vivo might minimize fibrosis, thereby improving shunt function. We found that after 8 weeks in vivo, experimental shunt function was equivalent to the Baerveldt shunt, while there was less scarring with increased neovascularizatin. These findings suggest that ePTFE has potential as an improved, long-term alternative material for use in constructing glaucoma shunts.     

Modelling the postsynaptic location and magnitude of tonic conductance changes resulting from neurotransmitters or drugs

Tonic conductance changes, synaptically or drug-mediated, can occur near the soma, in one or more distal dendrites, or diffusely. Using simple analogue passive neuronal models, means of localizing tonic conductance changes from intrasomatic recordings were explored. The input resistance measured from the soma was more influenced by perisomatic than distal conductance changes. The membrane time constant, τ₀, was quite sensitive to shunt magnitude, but not to shunt location. Semilogarithmic plots of the voltage response to a short constant current pulse showed that proximal shunts caused a faster earlier decay than distal shunts. Combining these data it is often possible to estimate the location of a tonic conductance change in a neuron from intrasomatic recordings.     

Hylan gel composition for percutaneous embolization

Viscoelastic, pseudoplastic, radiopaque injectable hylan gel for percutaneous embolization was developed and evaluated by in vitro and in vivo tests. The embolization gel is composed of cross-linked hylan (hyaluronan, hyaluronate), tantalum, microcrystalline cellulose, hexamethonium chloride, and thrombin. Upon delivery through small-lumen catheters to the appropriate vascular site, the gel induces formation of a solid blood/gel coagulum. Results from animal studies (rat aorta, rabbit auricular artery) demonstrate that formation of complete and long-lasting arterial blockage is readily achievable without complications due to blood flow, partial vessel obstruction, uncontrolled polymerization, or movement of the gel or its components (specifically thrombin and hexamethonium chloride) into the circulation. Microscopic evaluation indicates that arterial occlusion initially occurs as a result of the injected gel and formed fibrin; at 7 weeks and beyond, arteries are occluded by injected gel, inflammatory cells and fibrosis (scar tissue).     

The clinical anatomy of congenital portosystemic venous shunts

Congenital portosystemic venous shunts are rare. Their gross anatomy has not been well defined. Four different varieties of congenital portosystemic venous shunts are described in six children seen during a 10-year period, focusing on the anatomy of the shunt as determined by imaging studies and surgery. A detailed review of the literature indicates that congenital portosystemic venous shunts are best classified as: extrahepatic or intrahepatic. Extrahepatic shunts may be further subdivided into portocaval shunts (type 1 end-to-side and type 2 side-to-side) and others. Intrahepatic shunts are due to an abnormal intrahepatic connection between the portal vein and hepatic vein/inferior vena cava or a persistent patent ductus venosus. Additional congenital anomalies, particularly cardiac malformations, may be associated with any type. Some congenital intrahepatic portosystemic venous shunts close spontaneously in infancy; all other congenital portosystemic venous shunts tend to remain patent. To a variable extent, depending largely on the volume and duration of the shunt, affected individuals are at risk of developing hepatic encephalopathy and/or an intrahepatic tumor. The key to understanding the pathogenesis of these shunts lies in the normal developmental mechanisms underlying the formation of the portal vein and inferior vena cava in the embryo.     

Surgery for variceal bleeding in cirrhosis: a review of our experience and present concepts.

The major cause of portal hypertension in Western countries is nutritional cirrhosis (parenchymal block) related to alcoholism. A third of those patients die of variceal bleeding when increased pressure within the varices precipitates bleeding. Construction of portal systemic shunts is aimed at reducing the pressure within the varices and thereby decreasing the risk of bleeding. However, it increases the incidence of hepatic encephalopathy and hence should be used only in patients who have bled. The remaining function appears to be the main factor that determines survival and the incidence of encephalopathy in obese individuals. Portacaval shunts almost completely eliminate the risk of bleeding. There is a greater incidence of hepatic encephalopathy with this procedure than with other shunts. The splenorenal shunt and the distal splenorenal shunt appear to work well in selected patients. Technically, it is a more difficult procedure. The interposition mesocaval shunt is technically easier and is also helpful in patients with ascites. Its post-shunt encephalopathy rate, however, is higher than the splenorenal shunt or the distal splenorenal shunt, though less than the portacaval shunts. Experience with the newer arterialized portacaval and coronary caval shunts is limited. A non-shunt procedure, such as the one described by Sugiura, with impressive results and follow-up may become more acceptable as experience grows.     

Selective and total shunts in the treatment of bleeding varices. A randomized controlled trial.

Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).     

硫化氢供体对大鼠高肺血流性肺动脉高压中内皮素-1及结缔组织生长因子表达的影响

目的：探讨硫氢化钠（NaHS）对大鼠高肺血流性肺动脉高压中内皮素-1(ET-1)及结缔组织生长因子(CTGF)表达的影响。方法:32只雄性SD大鼠随机分为分流组（n=8）、分流+NaHS组（n=8）、假手术组（n=8）和假手术+NaHS组（n=8）。对分流组和分流+NaHS组大鼠行腹主动脉-下腔静脉穿刺建立高肺血流动物模型。分流11周后，分别测定大鼠肺动脉收缩压（SPAP）、血浆ET-1含量、肺组织硫化氢（H2S）含量、肺组织ET-1mRNA的表达及肺动脉CTGF蛋白的表达。结果:分流11周，大鼠SPAP明显高于假手术组(P<0.05)；分流组大鼠肺组织ET-1mRNA表达、血浆ET-1含量以及肺腺泡肌型动脉CTGF表达明显高于假手术组；肺组织H2S含量明显低于假手术组(P<0.05)；应用NaHS干预11周，分流+NaHS组大鼠H2S含量明显高于、而SPAP明显低于假手术组(P<0.05)；分流+NaHS组大鼠血浆ET-1含量及肺组织ET-1mRNA的表达明显低于分流组(P<0.05)；分流+NaHS组大鼠肺动脉CTGF蛋白表达明显低于分流组(P<0.05)。结论: NaHS可能通过降低血管活性肽ET-1 及CTGF在肺组织的表达参与调节高肺血流性肺动脉高压的形成。     

Age-related changes in plasma immunoreactive growth hormone secretory patterns in broiler pullets

Apparent circulating plasma immunoreactive growth hormone (I-GH) concentrations were determined in Hubbard X Hubbard broiler pullets at weekly intervals from 1 through 12 weeks of age, in conjunction with measurement of relative weight gain (growth rate). Blood was obtained by cardiac puncture (wk 1) or venipuncture (weeks 2-12) from 12 birds (one sample per bird) at each age. Subsequently, in a second study, the growth hormone secretory pattern was quantitated for broiler pullets at 4, 8 and 12 weeks of age. At each of these ages, five birds were surgically prepared with indwelling venous catheters and blood samples withdrawn remotely at 15 or 30 min intervals for 6 h beginning at 0900 h. Plasma was assayed for I-GH and data subjected to a computer-based statistical algorithm for quantitation of secretory pattern characteristics. Plasma I-GH increased with age to peak at 4 weeks and declined thereafter, whereas relative weight gain declined overall. When adjusted for increasing body weight, however, plasma I-GH concentration per unit metabolic body size (an expression of relative tissue exposure to the hormone) was highly correlated with growth rate (P less than .007). At 4 weeks of age, chicks displayed relatively high amplitude peaks in plasma I-GH (35.0 +/- 3.20 ng/ml) (means +/- SEM) which occurred asynchronously between birds. These peaks were substantially reduced in amplitude (P less than .05) by 8 weeks (5.9 +/- 2.82 ng/ml) and remained low through 12 weeks of age (2.6 +/- 1.18 ng/ml). The baseline plasma concentration of I-GH also declined (P less than .05) from 4 to 8 weeks of age, and remained low thereafter. In contrast, the frequency and duration of peaks did not differ significantly with age, such that peaks occurred approximately every 1.75 h and were 1 h in duration, over all ages. These age-related changes in secretory pattern characteristics, and the strong association between plasma I-GH per unit of metabolic body size and growth rate, suggest that both pattern and level of tissue exposure may be important in the regulation of growth in these birds.     

Immunomorphological study of angiotensin-converting enzyme in coronary shunts

Coronary bypass surgery is the operation of choice in patients with coronary atherosclerosis. However, some time later, venous shunts frequently stop functioning after successful surgery. The reasons for this include intimal hyperplasia occurring in response to release of cytokines, angiotensin II in particular. In man, the latter is formed by angiotensin-converting enzyme or chimase. The findings show that elevated ATF concentrations are found in some cells in the area of intimal hyperplasia, in macrophages and smooth muscle cells of the shunt hyperplastic intima. The increased ATF concentration in the aorto-coronary shunt cells results in the elevated levels of angiotensin II, the migration of smooth muscle cells, their hypertrophy and hyperplasia, the formation of atherosclerotic plaques, thrombosis, and circulatory disorders.     

Central cardiovascular shunts in the perinatal marsupial

Background. Marsupials are born at an early stage of development after a short period of gestation. In this study the nature and timing of closure of the central cardiovascular shunts was investigated. Methods. Light and scanning electron microscopy were used to determine changes in central cardiovascular shunts in eight marsupial species with gestation periods of between 12.5 and 36.5 days and birth weights ranging from 12.5 mg to 740 mg. Laboratory mice with a birth weight of about 1,000 mg and a gestation period of 21 days were included for comparison. Results. Marsupials have a ductus arteriosus and an interatrial communication. The former closes rapidly after birth in the marsupial; however the interatrial communication is in the form of a fenestrated septum, which closes as result of tissue proliferation over a period of days after birth. An additional central shunt, an interventricular foramen, was found to persist in three species for a short time after birth. In one species, the eastern native cat, Dasyurus viverrinus, which has a gestation period of about 19 days and low birth weight of about 12.5 mg, in addition to the two common shunts there was a large interventricular communication and septation of the outflow tract was incomplete. Conclusion. In adapting from intra-uterine life, it seems that marsupials have adopted different, but equally effective strategies, with regard to the circulatory system. © 1995 Wiley-Liss, Inc.