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Focused transhepatic electroporation mediated by hypersaline infusion through the portal vein in rat model. Preliminary results on differential conductivity

Clara Pañella
Clara Pañella
, 
Quim Castellví
Quim Castellví
, 
Xavier Moll
Xavier Moll
, 
Rita Quesada
Rita Quesada
, 
Alberto Villanueva
Alberto Villanueva
, 
Mar Iglesias
Mar Iglesias
, 
Dolores Naranjo
Dolores Naranjo
, 
Patricia Sánchez-Velázquez
Patricia Sánchez-Velázquez
, 
Anna Andaluz
Anna Andaluz
, 
Luís Grande
Luís Grande
, 
Antoni Ivorra
Antoni Ivorra
 and 
Fernando Burdío
Fernando Burdío
   | Nov 29, 2017
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Article Category: Research Article
Published Online: Nov 29, 2017
Page range: 415 - 421
Received: Jul 02, 2017
Accepted: Oct 22, 2017
DOI: https://doi.org/10.1515/raon-2017-0051
© 2017 Clara Pañella, Quim Castellví, Xavier Moll, Rita Quesada, Alberto Villanueva, Mar Iglesias, Dolores Naranjo, Patricia Sánchez-Velázquez, Anna Andaluz, Luís Grande, Antoni Ivorra and Fernando Burdío
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Figure 1

IRE application model with plate electrodes, in scattered tumoural liver without (A) or with (B) hypersaline infusion through the portal vein and its corresponding numerical simulation (C and D) obtained from the received electric field in healthy and tumoural tissue - own results obtained from our previous research (17, 18). (C) Without hypersaline infusion through the portal vein, there is not selective effect on scattered tumoural nodules. Nevertheless, in (D) with hypersaline infusion through the portal vein, there is an increase on the electric field on scattered tumours (meaning a preferential ablative IRE effect on these nodules) because of the increase in healthy tissue conductivity (σ).
IRE application model with plate electrodes, in scattered tumoural liver without (A) or with (B) hypersaline infusion through the portal vein and its corresponding numerical simulation (C and D) obtained from the received electric field in healthy and tumoural tissue - own results obtained from our previous research (17, 18). (C) Without hypersaline infusion through the portal vein, there is not selective effect on scattered tumoural nodules. Nevertheless, in (D) with hypersaline infusion through the portal vein, there is an increase on the electric field on scattered tumours (meaning a preferential ablative IRE effect on these nodules) because of the increase in healthy tissue conductivity (σ).

Figure 2

General setting of the hypersaline infusion protocol through the portal vein in Sprague Dawley rats (A) and in Athimic rats with implanted tumour (B). After exposing spleen at abdominal midline, hypersaline infusion was performed by trans-splenic puncture with a pump. Hyposaline infusion through the jugular vein was performed to compensate the systemic hypernatremia. Two tetrapolar setup electrodes measured tumour and healthy hepatic conductivity and data were collected with a multi-frecuency device and gathered in a computer.
General setting of the hypersaline infusion protocol through the portal vein in Sprague Dawley rats (A) and in Athimic rats with implanted tumour (B). After exposing spleen at abdominal midline, hypersaline infusion was performed by trans-splenic puncture with a pump. Hyposaline infusion through the jugular vein was performed to compensate the systemic hypernatremia. Two tetrapolar setup electrodes measured tumour and healthy hepatic conductivity and data were collected with a multi-frecuency device and gathered in a computer.

Figure 3

Conductivity changes after hypersaline infusion protocol in a representative case of group A (Sprague Dawley) and B (Athimic rats with implanted tumour). In both groups, a sharp increase and a posterior slowing decrease of conductivity in healthy hepatic tissue was observed. On the contrary, conductivity of the tumoural tissue (Group B) was stable. Thus, it created a therapeutic window (TW), the safety period where IRE it would be applied.
Conductivity changes after hypersaline infusion protocol in a representative case of group A (Sprague Dawley) and B (Athimic rats with implanted tumour). In both groups, a sharp increase and a posterior slowing decrease of conductivity in healthy hepatic tissue was observed. On the contrary, conductivity of the tumoural tissue (Group B) was stable. Thus, it created a therapeutic window (TW), the safety period where IRE it would be applied.

Figure 4

These were representative livers from group A (Sprague Dawley) and group B (Athimic rats with implanted tumour) after HI protocol at the 4th week of postoperative. Histological analysis revealed the indemnity of the architecture and morphology of healthy hepatocytes (H) of both groups A and B. In group B, histological samples showed that HI protocol did not interfere in tumour (T) evolution.
These were representative livers from group A (Sprague Dawley) and group B (Athimic rats with implanted tumour) after HI protocol at the 4th week of postoperative. Histological analysis revealed the indemnity of the architecture and morphology of healthy hepatocytes (H) of both groups A and B. In group B, histological samples showed that HI protocol did not interfere in tumour (T) evolution.

Comparison between two groups A (Sprague Dawley) and B (Athimic). *PO: Postoperative

GROUP Ap-valueGROUP Bp-value
Administration of HI protocoln= 9n=8
Weight increase during PO* (grams)100±30.570.012-1.94±37.810.386
Baseline Conductivity in healthy tissue (S/m)0.10±0.020.13±0.02
Conductivity after HI in healthy tissue (S/m)0.27±0.750.0080.49±0.170.008
Baseline Conductivity in tumour tissue (S/m)NA0.24±0.03
Therapeutic window (sec)NA175±115
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