Surgical attenuation of congenital portosystemic shunts in dogs. Techniques, complications and prognosis

Abstract

The general aim of this thesis was to identify factors associated with outcome after surgical attenuation of congenital portosystemic shunts (CPSS) in dogs and to clarify underlying mechanisms of postoperative recovery in this disease. Two surgical techniques used for CPSS attenuation, ligation and cellophane banding, were evaluated in 97 and 106 dogs, respectively. Cellophane banding resulted in less short-term complication and mortality rates in dogs with extrahepatic shunts. In intrahepatic shunts, cellophane banding resulted in higher complication and mortality rates than in extrahepatic CPSS. After CPSS ligation, no differences in mortality between dogs with intrahepatic or extrahepatic CPSS were found. With either technique a small proportion of dogs did not recover completely. Surgical technique is apparently not the most important factor that defines long-term outcome. After CPSS ligation, the achieved degree of closure was negatively associated with mortality. In dogs with extrahepatic shunts, both variables were correlated with the diameter of the portal vein. CPSS seems to be not only a disease of an additional abnormal vessel, but also a disease that affects the normal portal vasculature. Unexpectedly, long-term outcome did not depend on the degree of CPSS closure or on portal development at the time of surgery. Because haemorrhage was an important complication after CPSS ligation, haemostasis was evaluated in 34 dogs with a CPSS. These dogs had lower preoperative platelet counts, lower activity of clotting factors II, V, VII, X, an increased activity of factor VIII and a prolonged activated partial thromboplastin time compared to healthy dogs. Immediately after CPSS attenuation, platelet counts and the activity of clotting factors I, II, V, VII, IX, X, and XI were further decreased, and prothrombin time became prolonged. In dogs with complete recovery of shunting, haemostasis was normalized after 6 weeks, in contrast to dogs with persistent shunting. In dogs with CPSS, outcome after shunt attenuation is possibly associated with hepatocyte and portal vein proliferation. Liver size and hepatic growth following surgical attenuation of a CPSS were evaluated in 10 dogs. At 2 months after surgery, median liver size had increased from 18.2 to 28.2 cm3/kg body weight. The intraoperative hepatic expression of 19 genes involved in hepatic and vascular growth and fibrosis was evaluated in 48 dogs with a CPSS in relation to postoperative outcome. Increased mRNA expression of MAT2a (methionine adenosyltransferase 2 alpha) and HGFac (hepatocyte growth factor activator) were associated with good recovery. A model including both genes predicted outcome after CPSS ligation correctly in 75% of the dogs. Low MAT2a may partially explain the poorer prognosis of intrahepatic CPSS compared to extrahepatic CPSS. To identify genes that are differently expressed between dogs with different outcome after CPSS attenuation, microarray analyses were performed in liver tissue of 46 dogs with a CPSS. Sixty-three genes were differently expressed, including several genes that may directly affect postoperative recovery. Further studies are essential to confirm and validate these findings. Clarification of factors that define postoperative outcome may help to predict treatment response and provide additional forms of treatment.