Adenoviral transfer in the liver: a novel in vivo simulation model in the rat

Abstract

BACKGROUND: Established in vivo models for adenoviral transfer are limited due to a restricted time-period for application of pharmaceutical substances, problems in selective targeting of organs, and artificial lesions of the targeted organ because of the method itself. Therefore, we developed a liver circulation model to avoid these difficulties. METHODS: Male Lewis-(RT1)-rats (n = 8) with a body weight of 120 g received median laparotomy under isoflurane anesthesia. After exposition of the coeliac trunk and the inferior vena cava the right renal vein was punctured. Next the abdominal aorta, the splenic artery, the left gastric artery, and the gastroduodenal artery were simultaneously clamped and intravenous infusion of methylene blue into the right renal vein was started. RESULTS: Due to the selective application of the agent into the liver we could demonstrate an obvious discoloration of the liver in this setting, whereas all other abdominal organs were not affected. Photometric extinction of cell suspensions of liver biopsies revealed a maximum concentration of methylene blue 30 min after injection (0.890–2.300 mM). As expected, no extinction was found in cell suspensions of other organs. CONCLUSIONS: Our experimental setting represents a reproducible, reversible, and easily practicable model for semi-selective in vivo application of pharmaceutical substances into the liver. Therefore, this approach enables the in vivo adenoviral transfer of cytoprotective agents or chemotherapeutic drugs selectively into the liver.