title: Electrochemical treatment: An investigation of dose-response relationships using an isolated liver perfusion model.
abstract: OBJECTIVE
  Ablative techniques such as radiofrequency ablation or non-thermal electrochemical treatment (ECT) are used to manage unresectable liver metastases. Although ECT is not affected by the cooling effect from adjacent vessels, there is a paucity of data available on ECT.
  
  
  METHODS
  We used porcine livers to establish an organ model with portal venous and hepatic arterial blood flow for a standardized analysis of the relationship between dose (electric charge) and response (volume of necrosis).
  
  
  RESULTS
  This model allowed us to study pressure-controlled perfusion of portal venous and hepatic arterial circulation in the absence of a capillary leak. A specially designed guiding template helped us place platinum electrodes at reproducible locations. With two electrodes, there was a linear relationship between charges of no more than 200 C and necrosis. The relationship was logarithmic at charges of 400-600 C. Larger electrode spacing led to a significant increase in necrosis. We measured pH values of 0.9 (range: 0.6-1.3) at the anode and 12.6 (range: 11.6-13.4) at the cathode.
  
  
  CONCLUSIONS
  Using a perfusion model, we established an experimental design that allowed us to study ECT in the liver of large animals without experiments on living animals. An electrode template helped us improve the standardized analysis of dose-response relationships. ECT created reproducible and sharply demarcated areas of necrosis, the size of which depended on the charge delivered as well as on the number and spacing of electrodes. Doses higher than 600 C require longer treatment times but do not increase the area of necrosis (logarithmic dose-response relationship).
authors.affiliation: Department of Surgery, University of Luebeck Medical School, Ratzeburger Allee 160, Luebeck, Germany. ralf_czymek@web.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Czymek
authors.forename: Dorothea
authors.initials: D
authors.lastname: Dinter
authors.forename: Stephan
authors.initials: S
authors.lastname: Löffler
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gebhard
authors.forename: Tilman
authors.initials: T
authors.lastname: Laubert
authors.forename: Andreas
authors.initials: A
authors.lastname: Lubienski
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D015314:Dialysis Solutions / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055664:Electrochemical Techniques / Q000379:methods*; D005112:Extracorporeal Circulation / Q000379:methods*; D005500:Follow-Up Studies; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009336:Necrosis / Q000517:prevention & control; D010477:Perfusion / Q000379:methods*; D013552:Swine
chemical_list: D015314:Dialysis Solutions