Novel H-shunt Venovenous Bypass for Liver Transplantation in Cynomolgus Macaques.

Cynomolgus monkeys are often used in preclinical transplantation research. Performing liver transplantation in cynomolgus monkeys is challenging because they poorly tolerate portal vein clamping during the anhepatic phase. Finding an alternative to portal vein clamping is necessary before preclinical liver transplant models can be performed with reliable outcomes. We used 3 different techniques to perform 5 liver transplants in male cynomolgus macaques (weight, 7.4-10.8 kg; mismatched for MHC I and II; matched for ABO). In procedure A, we clamped the portal vein briefly, as in human transplants, as well as the superior mesentery artery to minimize congestion at the expense of temporary ischemia (n = 2). In procedure B, we performed a temporary portocaval shunt with extracorporeal venovenous bypass (n = 1). For procedure C, we developed an H-shunt system (modified portocaval shunt) with extracorporeal bypass (n = 2). Postoperative immunosuppression comprised cyclosporine A, mycophenolate mofetil, and steroids. Recipients in procedure A developed hemodynamic instability and were euthanized within 2 d. The recipient that underwent procedure B was euthanized within 11 d due to inferior vena caval thrombosis. The H-shunt in procedure C led to minimal PV congestion during the anhepatic phase, and both recipients reached the 21-d survival endpoint with good graft function. Our novel H-shunt bypass system resulted in successful liver transplantation in cynomolgus macaques, with long-term posttransplant survival possible. This technical innovation makes possible the use of cynomolgus monkeys for preclinical liver transplant tolerance models.

Derivaciones portosistemáticas congénitas: reporte de caso en un canino / Congenital portosystemics shunts: case report in a dog

Las derivaciones portocava extrahepáticas son anomalías vasculares donde la circulación portal se conecta con la circulación sistemática. En los caninos constituyen el 45% de las anomalías portovasculares, registrándose un predisposición racial. El objetivo de este trabajo es presentar los hallazgos ecográficos en un canino de raza Yorkshire. Se observó disminución del tamaño hepático, con la presencia de un vaso anómalo que comunicaba la vena porta con la vena cava, y donde el Doppler color registró turbulencia. Luego de la corrección quirúrgica, se observó un aumento del diámetro de la vena porta, con aumento del tamaño del órgano. En el diagnóstico de las derivaciones vasculares extra hepáticas, la ecografía tiene la ventaja de ser un método no invasivo que da información sobre el parénquima hepático y la vasculatura, sirviendo de guía para la selección de los procedimientos quirúrgicos.

Derivaciones portosistemáticas congénitas: reporte de caso en un canino / Congenital portosystemics shunts: case report in a dog

Las derivaciones portocava extrahepáticas son anomalías vasculares donde la circulación portal se conecta con la circulación sistemática. En los caninos constituyen el 45% de las anomalías portovasculares, registrándose un predisposición racial. El objetivo de este trabajo es presentar los hallazgos ecográficos en un canino de raza Yorkshire. Se observó disminución del tamaño hepático, con la presencia de un vaso anómalo que comunicaba la vena porta con la vena cava, y donde el Doppler color registró turbulencia. Luego de la corrección quirúrgica, se observó un aumento del diámetro de la vena porta, con aumento del tamaño del órgano. En el diagnóstico de las derivaciones vasculares extra hepáticas, la ecografía tiene la ventaja de ser un método no invasivo que da información sobre el parénquima hepático y la vasculatura, sirviendo de guía para la selección de los procedimientos quirúrgicos.(AU)

Re-evaluation of a portocaval venograft without an ameroid constrictor as a method for controlling portal hypertension after occlusion of intrahepatic portocaval shunts in dogs.

OBJECTIVE: To evaluate the use of a portocaval venograft without an ameroid constrictor in the surgical management of intrahepatic portosystemic shunts (PSS). STUDY DESIGN: Prospective clinical study. ANIMALS: Seven dogs with intrahepatic PSS. METHODS: Portal pressure was measured after temporary suture occlusion of the intrahepatic PSS. In dogs with an increase in portal pressure > or =8 mm Hg or signs of portal hypertension, a single extrahepatic portocaval shunt was created using a jugular vein. Clinical outcome and complications were recorded. RESULTS: The mean (+/-SD) portal pressure increased from 5.9+/-1.6 to 17.9+/-4.1 mm Hg with PSS occlusion. There were no intraoperative complications and, after creation of the portocaval shunt, the intrahepatic PSS could be completely ligated in all dogs. The final portal pressure was 9.6+/-1.9 mm Hg. Complications developed during postoperative hospitalization in 5 dogs and included incisional discharge (4 dogs), ascites (3), ventricular premature contractions (2), and melena, bloody diarrhea, neurologic signs, coagulopathy, and aspiration pneumonia (each in 1 dog). Six dogs died or were euthanatized with clinical signs related to depression, inappetance, abdominal pain, vomiting, melena, and abdominal distention, with a median survival of 82 days (range, 20-990 days). One dog was clinically normal at 33 months after surgery. CONCLUSIONS: Clinical signs observed in 6 dogs after surgery were consistent with portal hypertension. Use of a portocaval venograft without an ameroid constrictor may reduce the likelihood of hepatic vascular development, thereby increasing the risk of life-threatening portal hypertension should the venograft suddenly occlude. CLINICAL RELEVANCE: Use of a portocaval venograft without an ameroid constrictor to control portal hypertension after ligation of an intrahepatic PSS cannot be recommended.

Idiopathic noncirrhotic portal hypertension in dogs: 33 cases (1982-1998).

OBJECTIVE: To describe clinical signs, diagnostic findings, and outcome in dogs with idiopathic intrahepatic portal hypertension. DESIGN: Retrospective study. ANIMALS: 33 dogs. PROCEDURE: Medical records of dogs with portal hypertension of intra-abdominal origin were reviewed. Dogs with intra-abdominal portal hypertension of vascular causes or with hepatic histopathologic changes consistent with severe diffuse hepatobiliary disease were excluded. History and results of physical examination, clinicopathologic tests, diagnostic imaging studies, histologic examination, and treatment were summarized. Outcome was determined in 26 dogs. RESULTS: Dogs were referred most often because of ascites, intermittent vomiting or diarrhea, and polydipsia of several months' duration. Microcytosis, high serum alkaline phosphatase and alanine transaminase activities, hepatic dysfunction, urine specific gravity < or = 1.021, and abdominal transudate were the predominant clinicopathologic features. Microhepatia, abdominal effusion, and multiple anomalous venous anastomoses were the major findings of diagnostic imaging. Hepatic histopathologic changes were consistent with idiopathic noncirrhotic portal hypertension and were indistinguishable from those of dogs with surgically created portocaval anastomosis. Outcome was determined for 19 dogs released from hospital; 13 dogs remained healthy with mostly palliative treatment for periods of 5 months to 9 years. CONCLUSIONS AND CLINICAL RELEVANCE: The clinical signs, clinicopathologic test results, portal pressure, and gross appearance of the liver of dogs with idiopathic noncirrhotic portal hypertension may be identical to those of dogs with cirrhosis; therefore liver biopsy is crucial. Because the prognosis for idiopathic noncirrhotic portal hypertension is generally favorable, owners of affected dogs should be discouraged from choosing euthanasia.

A method for controlling portal pressure after attenuation of intrahepatic portacaval shunts.

Two dogs had right divisional intrahepatic portacaval shunts within the right lateral lobe of the liver. In both dogs, an extrahepatic portacaval vascular anastomosis was created, using an autologous right external jugular vein graft. The intrahepatic shunts were completely attenuated using a prehepatic intravascular caval approach. The creation of the vascular graft allowed postattenuation rises in portal pressure to be controlled, preventing the development of life threatening portal hypertension. Both dogs recovered from the procedure. One dog is clinically normal and does not require medication (8 months postoperatively); the other dog was euthanatized 5 months after surgery because of renal failure. Scintigraphy studies, performed before surgery, showed significant shunting of portal blood away from the liver (shunt indices 65% and 59%), whereas, similar studies done 4 weeks afterwards showed almost normal portal blood flow (shunt indices 16% and 18%, respectively).

Postcaval thrombosis and delayed shunt migration after pleuro-peritoneal venous shunting for concurrent chylothorax and chylous ascites in a dog.

Simultaneous chylothorax and chylous ascites related to intestinal lymphangiectasia was diagnosed in a 4-year-old spayed female dog. Palliative pleural and peritoneal drainage was accomplished by placement of fenestrated silastic sheeting into surgically created diaphragmatic defects, and implantation of a pleuro-peritoneal venous shunt. The immediate postoperative period was complicated by acute renal failure secondary to postcaval thrombosis originating at the site of placement of the efferent pump catheter and extending to the level of the renal veins. Rapid resolution of this complication was accomplished with systemic anticoagulation. Clinical signs related to fluid accumulation resolved for 10 weeks after which acute decompensation occurred and the dog was euthanatized. Postmortem examination showed that reaccumulation of fluid was associated with migration of the efferent limb of the shunt from the caudal vena cava.

Surgical creation of portacaval shunts during temporary intestinal arterial and venous occlusion in dogs.

OBJECTIVE: To surgically create complete portacaval shunts in dogs during temporary arrest of intestinal arterial and portal venous blood flow. DESIGN: Complete portacaval anastomoses were surgically created, and liver function was evaluated for 14 to 18 weeks after surgery. ANIMALS: 32 adult mixed-breed dogs of either sex. PROCEDURE: Administration of deferoxamine and temporary intestinal arterial occlusion were used to minimize the intestinal cellular damage resulting from the complete, temporary arrest of portal venous blood flow during creation of the portacaval anastomosis. Side-to-side, appositional anastomoses ( > 2 cm diameter) were formed between the portal vein and caudal vena cava. Dogs were observed daily for signs of hepatic encephalopathy, and food intake was recorded. Body weight was recorded weekly. Preprandial plasma ammonia, serum urea nitrogen, and glucose concentrations and sulfobromophthalein retention were measured monthly. The dogs were euthanatized, and necropsy was performed 14 to 18 weeks after surgery. RESULTS: 30 of 32 dogs recovered without complications. Complete portosystemic shunting was documented by increased plasma ammonia concentration, decreased serum urea nitrogen and glucose concentrations, prolonged sulfobromophthalein retention (P < 0.01), and inspection at necropsy. CONCLUSION: This method of providing temporary, complete arrest of portal venous blood flow was helpful in allowing accurate, appositional portacaval anastomoses to be created that remained patent for 14 to 18 weeks. CLINICAL RELEVANCE: This method of providing temporary, complete arrest of portal venous blood flow may prove useful in clinical surgery when temporary arrest of portal blood flow is desired.

Transvenous retrograde angiography for detection of portal-caudal caval shunt.

A retrograde angiography method for the detection of a portosystemic shunt was studied. The retrograde angiography was done by compressing the caudal vena cava in the chest by applying pressure to the thoracic cavity, then feeding a contrast medium into the caudal vena cava without releasing the pressure loading. The angiography could detect shunt vessels in experimental cases as well as clinical cases. This method is useful for the confirmation of a portal-caudal caval shunt, which can be performed without technical difficulty and without the need for a special kind of catheter.

Microcytosis and iron status in dogs with surgically induced portosystemic shunts.

Microcytosis is common in dogs with congenital portosystemic shunts (PSS) and acquired liver disease. The objective of this study was to determine if microcytosis could be induced in normal dogs by surgical creation of PSS, and to characterize the changes in hematology and iron status. Hematocrit, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration decreased linearly from 45.5%, 69.1 fL, 22.8 g/dL and 33.1% to 39.5%, 55.9 fL, 17.8 g/dL and 31.9%, respectively, 18 weeks after creation of PSS. The erythrocyte count did not change, but red cell distribution widths indicated a shift to a heterogenous population with decreased volume. Mean cell volume and mean cell hemoglobin decreased rapidly after induction of PSS and were significantly (P < .05) different from presurgery values within 2 weeks. Serum iron and copper concentrations and total iron binding capacity were decreased in dogs with PSS. Liver iron concentration doubled after creation of PSS, with the majority of stainable iron located in Kupffer cells. The changes in erythrocyte indices and measures of iron status in dogs with surgically induced PSS were similar to those in dogs with congenital PSS. Microcystosis developed rapidly in dogs after induction of PSS. These results indicate that iron deficiency was not the cause of microcytosis in these dogs.

Effect of bedding changes and room ventilation rates on blood and brain ammonia levels in normal rats and rats with portacaval shunts.

Normal rats and rats with portacaval shunts were exposed to low concentrations of atmospheric ammonia generated from decomposing urine and feces. The ammonia concentration in the atmosphere was varied by altering the effective ventilation rate, animal density in the enclosure, and bedding change frequency. Atmospheric ammonia concentrations in the animal holding areas varied inversely with the frequency of bedding change and the rate of air exchange. Significant differences were found between normal and shunted animals in blood ammonia and alkaline phosphatase; brain ammonia, glutamate, and glutamine; and body weight. However, these alterations were the same regardless of the atmospheric ammonia concentration; there were no differences within the control group or shunted group housed in the different conditions. The findings suggest that in the range of ammonia concentrations in this study (0 to 9 ppm), ammonia taken in through the respiratory tract is not accumulated in the body to any significant extent.

A caval clamp for portacaval shunt in the rat.

An inexpensive caval clamp and stand, designed for use in the performance of portacaval shunt in the rat are described.

Indocyanine green clearance and ammonia tolerance in partially hepatectomized and hepatic devascularized, anesthetized dogs.

Indocyanine green clearance and ammonia tolerance were measured in anesthetized dogs with 60% hepatectomy, 40% hepatectomy, portacaval shunt, and hepatic artery ligation. With a dose of 0.5 mg of indocyanine green/kg of body weight, plasma clearance of the dye was significantly (P less than 0.001) delayed only in dogs with 60% hepatectomy. Ammonia tolerance was abnormal in dogs in this group, because after they were given a gastric challenge load of an ammonium salt, they had a 5-fold increase in plasma ammonia concentration, compared with a 2.5-fold increase in the control group. Before challenge loading, base-line plasma ammonia concentration was significantly (P less than 0.05) increased within 5 minutes after surgical preparation of the portacaval shunt. After challenge loading the stomach with an ammonium salt, dogs with portacaval shunt had increased plasma ammonia concentration, but the amount was not significantly different from postchallenge-loading values in control dogs. Dogs with 40% hepatectomy and with hepatic artery ligation could not be differentiated from control dogs by indocyanine green clearance or by ammonia tolerance testing. Abnormal tolerance to a challenge gastric load of an ammonium salt or delayed clearance of indocyanine green may indicate marked loss of functional hepatic mass, but normal tolerance or normal dye clearance may not exclude liver disease or dysfunction. Seemingly, base-line plasma ammonia concentration was a sensitive indicator of abnormal portal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)