Cytokine response of electrolytic ablation in an ex vivo perfused liver model

Gravante, Gianpiero; Ong, Seok Ling; Metcalfe, Matthew S.; Sorge, Roberto; Overton, John D.; Lloyd, David M.; Maddern, Guy J.; Dennison, Ashley R.

doi:10.1111/j.1445-2197.2010.05380.x

Cited by 12 publications

(10 citation statements)

References 22 publications

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“…Comparable to our previous liver ex vivo perfusion models 13,14 , the outcome of our liver ex vivo perfusion model showed similar changes in the liver physiology, biochemical, immunologic, and pathological findings 2,3,5,11 , to those more expensive in vivo studies and this confirm our model is reliable and economical acceptable model for the study of porcine liver and related pathology.…”

Section: Discussionsupporting

confidence: 62%

“…In the last few years our group has achieved considerable experience using an ex vivo porcine model to study the hepatic physiology 5,11 , new liver ablation techniques 2,5 , and liver immunology 3 . Despite the technical challenges derived from an additional organ, corrections of hyperglycemia, electrolytes imbalances and acid base changes were significant 7 and have lead the way to more complex experiments that require strict homeostatic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, maintaining normal physiological and biochemical parameters for a prolonged period requires a closely monitored perfusion method and model. We have previously described our ex vivo autologous perfused porcine liver model for the study of hepatic physiology and significant progress has been achieved, since we began our liver reperfusion ex vivo model in 2005, in areas such as harvesting technique, understanding hepatic artery anatomical variations 1 , inflammatory response 2,3 , histological changes following liver electrolytic ablation (EA) 4 , and changes in acid base balance during EA 5 . Unfortunately hyperglycemia and metabolic acidosis require external supplements of insulin and bicarbonate to maintain an accurate physiological environment.…”

Section: Introductionmentioning

confidence: 99%

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Steps for the Autologous <em>Ex vivo</em> Perfused Porcine Liver-kidney Experiment

Chung

Eltweri

Isherwood

et al. 2013

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The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved postmortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow. Video LinkThe video component of this article can be found at

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Steps for the Autologous <em>Ex vivo</em> Perfused Porcine Liver-kidney Experiment

Chung

Eltweri

Isherwood

et al. 2013

JoVE

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“…Since 2007 our group has adapted the harvesting technique to improve the organ perfusion according to the variations of the porcine hepatic arterial supply [15] and has conducted various studies to investigate the inflammatory, biochemical and histological modifications during the ex vivo perfusions [1,3,11,12,14]. From the beginning it was evident that different metabolic products tended to accumulate in the circuit over the hours despite our efforts to control the biochemical milieu by administering counteracting substances (i.e., bicarbonate and insulin) [11,14].…”

Section: Introductionmentioning

confidence: 97%

“…Compared to more common in vivo animal experiments or ex vivo non perfused organs, the ex vivo perfused liver circuits provided models for the study of liver physiology [1], pathologic conditions (i.e., liver ischaemia during transplantation, liver failure, hepatic resections or traumas) [2][3][4][5][6][7][8], normothermic preservation of harvested organs [6,9,10], or ablative techniques [11][12][13]. The advantage of the ex vivo circuit compared to the in vivo counterparts is to provide a model disconnected from systemic neurological, hormonal or chemical influences and, therefore, simplify the evaluation of the hepatic intrinsic response to different stimuli [14].…”

Section: Introductionmentioning

confidence: 99%

The “kidney–liver” multiorgan ex vivo perfused model improves the circuit’s biochemical milieu during perfusion compared to the “liver–kidney” counterpart

et al. 2015

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The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu.

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Addition of a kidney to the normothermic ex vivo perfused porcine liver model does not increase cytokine response

et al. 2012

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The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.

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Cytokine response of electrolytic ablation in an ex vivo perfused liver model

Abstract: The ex vivo perfused liver model demonstrated changes in levels of IL-2, IL-4, IL-10 and TNF-alpha following hepatic EA.

Cited by 12 publications

References 22 publications

Steps for the Autologous <em>Ex vivo</em> Perfused Porcine Liver-kidney Experiment

Steps for the Autologous <em>Ex vivo</em> Perfused Porcine Liver-kidney Experiment

The “kidney–liver” multiorgan ex vivo perfused model improves the circuit’s biochemical milieu during perfusion compared to the “liver–kidney” counterpart

Addition of a kidney to the normothermic ex vivo perfused porcine liver model does not increase cytokine response

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