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Am J Physiol Renal Physiol. 2019 Sep 4. doi: 10.1152/ajprenal.00241.2019. [Epub ahead of print]

Extracorporeal Resuscitation with Carbon Monoxide Improves Renal Function by Targeting Inflammatory Pathways in Cardiac Arrest in Pigs.

Author information

1
Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
2
Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany, Germany.
3
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, United States.
4
Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Germany.
5
Department of Anesthesia and Critical Care, University Hospital Wuerzburg, Germany.
6
Department for Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
7
Department of Cardiovascular Surgery, University Heart Center, Faculty of Medicine, University of Freiburg, Germany.
8
Department of Pharmacy and Food Chemistry, Wuerzburg.
9
Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, Germany.

Abstract

BACKGROUND:

Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesize that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest.

METHODS:

Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional (CPR), an extracorporeal (E-CPR) or a CO-assisted extracorporeal (CO-E-CPR) protocol. CO was applied using a membrane-controlled releasing system. Markers of renal injury were measured and histopathological analyses were carried out. We investigated renal pathways involving inflammation as well as apoptotic cell death.

RESULTS:

No differences in serum neutrophil gelatinase-associated lipocalin (NGAL) were detected after CO treatment compared to Sham animals (Sham 71±7 and CO-E-CPR 95±6 ng/ml), while NGAL was increased in CPR and E-CPR groups (CPR 135±11 and E-CPR 124±5 ng/ml; p<0.05). Evidence for histopathological damage was abrogated after CO application. CO increased renal heat-shock protein 70 expression and reduced inducible cyclooxygenase 2 (CPR 60±8; E-CPR 56±8; CO-E-CPR 31±3 µg/ml; p<0.05). Caspase 3 activity was decreased (CPR 1469±276; E-CPR 1670±225; CO-E-CPR 755±83 pg/ml; p<0.05). Furthermore, we found a reduction in renal inflammatory signaling upon CO treatment.

CONCLUSION:

Our data demonstrates improved renal function by extracorporeal CO treatment in a porcine model of cardiac arrest. CO reduced pro-inflammatory and pro-apoptotic signaling, characterizing beneficial aspects of a novel treatment option to overcome high mortality.

KEYWORDS:

Acute Renal Failure; Carbon Monoxide; Cardiac Arrest; Extracorporeal Life Support; Ischemia-Reperfusion

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