Animal models

Effects of Blood Purification on Serum Levels of Inflammatory Cytokines and Cardiac Function in a Rat Model of Sepsis

Lin CM, Chen CR, Wu XQ, Ren JH, Chen SZ, Luo XF, Mei XQ, Shen LY, Guo MX, Ma XD, Yang T.
Blood Purif 2017: 44(1): 40-50

This sepsis rat model study explored the effects of blood purification, using a modified CytoSorb...

This sepsis rat model study explored the effects of blood purification, using a modified CytoSorb adsorber, on serum levels of inflammatory cytokines (IL6, TNF, IL10,) and cardiac function. The rat model of sepsis was established by cecal ligation and puncture. Rats were divided into normal control (n=8), sham operation (n=32), model (n=32), sham treatment (n=32), and BP treatment groups (n=32). Cardiac function, inflammatory cytokines, myocardial enzymes, pathological score of cardiac muscle tissue, and myocardial apoptosis of rats in each group were compared. Results showed that the sepsis rats had higher serum levels of inflammatory cytokines and lower cardiac function than those in the normal control and sham operation groups. Importantly, compared with the model and sham treatment groups, the CytoSorb treated group showed improved cardiac function, decreased inflammatory cytokines and myocardial enzymes, a lower pathological score, less myocardial apoptosis and a much lower mortality. The authors conclude that blood purification using CytSorb may reduce serum levels of inflammatory cytokines and improve cardiac function of septic rats.

Evaluation of the CytoSorb hemoadsorptive column in a pig model of severe smoke and burn injury.

Linden K, Scaravilli V, Kreyer SF, Belenkiy SM, Stewart IJ, Chung KK, Cancio LC, Batchinsky AI.
Shock. 2015 Nov;44(5):487-95

In this in vivo study in a porcine model of smoke inhalation and burn injury...

In this in vivo study in a porcine model of smoke inhalation and burn injury the authors aim to investigate the feasibility, technical safety and efficacy of cytokine and myoglobin removal by early use of CytoSorb.
Female Yorkshire pigs (n = 15) were injured by wood bark smoke inhalation and a 40% total body surface area deep burn and observed for 72 hours or death. The animals were randomized to hemoadsorption treatment (n = 9) or a sham treatment (n = 6) before injury and underwent a six hour hemoadsorption or sham session on days one, two and three. Serum cytokines (IL-1b, IL-6, IL-8, IL-10, TNF-alpha) and myoglobin were measured systemically, locally in bronchoalveolar lavage fluid and also in circulating blood before and after the adsorbing column resulting in a significant removal of IL-1b, IL-6, IL-10 and myoglobin across the device mainly during the first run, while systemic cytokine or myoglobin serum concentrations did not change.
The authors conclude that further investigations are needed to optimize the efficiency of mediator clearance to impact both circulating levels and clinically relevant outcomes.

Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model.

Peng ZY, Bishop JV, Wen XY, Elder MM, Zhou F, Chuasuwan A, Carter MJ, Devlin JE, Kaynar AM, Singbartl K, Pike F, Parker RS, Clermont G, Federspiel WJ, Kellum JA.
Crit Care. 2014 Jul 3;18(4):R141

In this in vivo study in a rat model of polymicrobial abdominal sepsis, the authors...

In this in vivo study in a rat model of polymicrobial abdominal sepsis, the authors investigate whether the removal of chemokines from the plasma changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues. The results of the study nicely demonstrate the efficacy of CytoSorb® to target leukocyte trafficking control by influencing chemokine gradients and thereby reducing leukocyte infiltration into remote healthy organs.

Role of cytokine hemoadsorption in cardiopulmonary bypass-induced ventricular dysfunction in a porcine model.

Vocelka CR, Jones KM, Mikhova KM, Ebisu RM, Shar A, Kellum JA, Verrier ED, Rabkin DG.
J Extra Corpor Technol. 2013 Dec;45(4):220-7.

This in vivo study in a porcine model undergoing cardiopulmonary bypass investigates the role of...

This in vivo study in a porcine model undergoing cardiopulmonary bypass investigates the role of hemoadsorption using CytoSorb on left ventricular function, cytokine removal, hemodynamics and noncardiac organ functions.

Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model.

Mikhova KM, Don CW, Laflamme M, Kellum JA, Mulligan MS, Verrier ED, Rabkin DG
J Thorac Cardiovasc Surg. 2013 Jan;145(1):215-24

This in vivo study investigates the effect of hemoadsorption (using CytoSorb) on cytokine levels (TNF...

This in vivo study investigates the effect of hemoadsorption (using CytoSorb) on cytokine levels (TNF, IL-6), cell injury (liver, kidney) and heart function (cardiac output, ventricular function) in a brain-dead porcine model.

Hemoadsorption Reprograms Inflammation in Experimental Gram-Negative Septic Peritonitis: Insights from In Vivo and In Silico Studies.

Namas RA, Namas R, Lagoa C, Barclay D, Mi Q, Zamora R, Peng Z, Wen X, Fedorchak MV, Valenti IE, Federspiel WJ, Kellum JA, Vodovotz Y
Mol Med. 2012 Dec 20;18:1366-74

This combined in vivo/in silico study in a rat model of E.coli-induced peritonitis investigates...

This combined in vivo/in silico study in a rat model of E.coli-induced peritonitis investigates whether hemoadsorption (usingCytoSorb) is able to reduce, relocalize and reprogram sepsis-induced acute inflammation (determined by analysis of 14 different cytokines and bacterial count in peritoneal fluid).

Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis

Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmelé T, Singbartl K, Federspiel WJ, Clermont G, Kellum JA
Kidney Int. 2012 Feb;81(4):363-9

This in vivo study in a subacute rat model of intraabdominal sepsis (cecal ligation puncture)...

This in vivo study in a subacute rat model of intraabdominal sepsis (cecal ligation puncture) investigates the effect of hemoadsorption (using CytoSorb®) that does not exert its positive effect as a direct reduction of cytokine plasma concentrations.  Levels of cytokines in this model are low, resulting in low removal by CytoSorb® (a concentration-dependent technology).  However, 7-day survival is significantly improved in the treatment group, with a reduction in latent organ injury.  Cytokine removal (TNFα, IL-1β, IL-6 und IL-10), organ injury/dysfunction (HMGB-1, ALT, and creatinine), production of cytokines (via NFkB binding in neutrophils) and 7-day survival is analyzed.  The effect of exchange blood transfusions (between CytoSorb-treated and sham animals) on IL-6 levels and 7-day mortality is also analyzed.

Effects of hemoadsorption on cytokine removal and short-term survival in septic rats

Peng ZY Carter MJ, Vellum JA
Crit Care Med. 2008 May;36(5):1573-7

In this in vivo study in a rat model of intraabdominal sepsis (cecal ligation and...

In this in vivo study in a rat model of intraabdominal sepsis (cecal ligation and puncture) the authors explore the effect of hemoadsorption (using CytoSorb) on cytokine adsorption (TNFα, IL-1β, IL-6 and IL-10), on mean arterial pressure (MAP) and short-term survival.

Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia.

Kellum JA, Song M, Venkataraman R.;
Crit Care Med. 2004 Mar;32(3):801-5.

This research article demonstrates that CytoSorb® hemoadsorption can improve short-term survival in a lethal endotoxin...

This research article demonstrates that CytoSorb® hemoadsorption can improve short-term survival in a lethal endotoxin challenge model of rat sepsis.  Investigators demonstrate a reduction in key cytokines and improve survival.  In addition, they demonstrate a reduction in NF-kB activity in hepatocytes taken from CytoSorb treated animals versus sham treated animals, suggesting the ability to not just remove cytokines, but to also down-regulate cytokine production.

Cytokine removal with a novel adsorbent polymer.

Song M, Winchester J, Albright RL, Capponi VJ, Choquette MD, Kellum JA.
Blood Purif. 2004;22(5):428-34.

This study characterizes the CytoSorb adsorbent polymer in terms of cytokine removal in 50 LPS...

This study characterizes the CytoSorb adsorbent polymer in terms of cytokine removal in 50 LPS challenged rats by measuringTNF alpha, interleukin 10 and interleukin 6 concentrations under a variety of conditions to evaluate adsorption kinetics. The authors found that all three cytokines were rapidly removed from the blood with less than 50% of the initial concentrations present after 1 h of circulation through the cartridge pointing towards a high efficiency, while binding is relatively unaffected by a variety of physical conditions.