Transcatheter Arterial Infusion with Heated Saline Changes the Vascular Permeability of Rabbit Hepatic Tumors

Rationale and Objectives The vascular permeability of tumors can be changed by transarterial infusion heat, but the mechanisms remain unknown. The aim of this study was to analyze the underlying causes of changes in tumor vascular permeability after heated perfusion via two different modes. Materials and Methods Thirty rabbits with VX2 hepatic tumors were randomly divided into three groups of 10 rabbits each. The hepatic artery was selectively catheterized via a femoral approach, and unheated saline (control group) or heated saline (60°C) was then injected in either a continuous (transcatheter arterial continuous perfusion [TACP]) or a pulsed (transcatheter arterial pulsed perfusion [TAPP]) manner. Changes in vascular permeability in the tumors were assessed using the following markers and methods: (1) qualitative assessment by visual estimation on digital subtraction angiography performed after the heat infusion procedure on live animals and quantitative assessment by spectrophotometry using Evans blue dye extravasation on tumor and liver tissue after animals were sacrificed and (2) kinase domain receptor or vascular endothelial growth factor (VEGF), expressed in vascular endothelial cells, assessed by immunohistochemical staining, Western blot analysis, and reverse transcription polymerase chain reaction. Results Tumor staining increased in the TAPP group more than in the TACP group, but not in the control group, assessed on digital subtraction angiography. Extracted dye was higher in tumors in the TAPP group than in those in the TACP group; extracted dye in both groups was higher than in the control group. Kinase domain receptor protein and messenger ribonucleic acid expression were both higher in the TAPP group than in the TACP and control groups. VEGF protein expression was lower in the TAPP and TACP groups than in the control group, but VEGF messenger ribonucleic acid expression was higher in the TACP group than in the TAPP and control groups, and VEGF messenger ribonucleic acid expression was lower in the TAPP group than in the control group. Conclusions The vascular permeability of rabbit VX2 tumors significantly increased after arterial pulsed heated infusion, and the protein kinase domain receptor may play a key role in this increase of tumor vascular permeability.