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Novel Leukocyte Modulator Device Reduces the Inflammatory Response to Cardiopulmonary Bypass

Johnston, Kimberly A.*; Westover, Angela J.*; Rojas-Pena, Alvaro†,‡; Haft, Jonathan W.†,§; Toomasian, John M.; Johnson, Thomas; Buffington, Deborah A.*; Humes, H. David*,¶,‖

doi: 10.1097/MAT.0000000000000822
Renal/Extracorporeal Blood Treatment
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Leukocyte (LE) activation during cardiopulmonary bypass (CPB) promotes a systemic inflammatory response that contributes to organ injury and postoperative organ dysfunction. A leukocyte modulatory device (L-MOD) for use during (and after) CPB to limit leukocyte-mediated organ injury was tested in a preclinical model. Twenty-two pigs underwent 180 minutes of CPB and 5 hours postoperative observation. Pigs received no intervention (group 1, n = 9), 3 hours of therapy by incorporation of L-MOD into the CPB circuit (group 2, n = 6), or 8 hours of therapy using a femoral venovenous L-MOD circuit during and after CPB (group 3, n = 7). Leukocyte activation was increased at the end of CPB and leukocyte counts, namely neutrophils, increased postoperatively in most animals. These indices trended much lower in group 3. Systemic vascular resistance was not as reduced post-CPB for the L-MOD-treated pigs, and urine output was significantly greater for group 3 (p < 0.01). At 5 hours post-CPB, group 3 had a lower troponin-I (1.59 ± 0.68 ng/ml) than group 1 or group 2 (3.97 ± 2.63 and 3.55 ± 2.04 ng/ml, respectively, p < 0.05) and a lower urine neutrophil gelatinase-associated lipocalin (7.57 ± 3.59 ng/ml) than the average of the other groups (50.71 ± 49.17, p < 0.05). These results demonstrate the therapeutic potential of L-MOD therapy to mitigate the inflammatory response to CPB. Eight hours of venovenous L-MOD resulted in less organ injury and post-op organ dysfunction in this model.

From the *Innovative BioTherapies, Inc, Ann Arbor, Michigan

Department of Surgery, Extracorporeal Life Support Laboratory (ECLS), University of Michigan, Ann Arbor, Michigan

Section of Transplantation Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan

§Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan

CytoPherx, Inc., Ann Arbor, Michigan.

Submitted for consideration October 2017; accepted for publication in revised form March 2018.

Disclosure: H. David Humes is a shareholder of Innovative BioTherapies and CytoPherx, Inc. biotechnology spin our companies of the University of Michigan. Kimberly A. Johnston, Angela J. Westover, and Deborah A. Buffington are employees of Innovative BioTherapies, Inc.

Funding: Support for the studies described in this manuscript was provided by the National Institutes of Health Small Business Innovation Research (SBIR) award number: 1R43HL127830-01.

Correspondence: H. David Humes, Innovative BioTherapies Incorporated, 650 Avis Road, Suite 300, Ann Arbor, MI 48108. E-mail: dhumes@innbio.com.

Copyright © 2019 by the American Society for Artificial Internal Organs