The Effect of Early Application of Synthetic Peptides 19-2.5 and 19-4LF to Improve Survival and Neurological Outcome in a Mouse Model of Cardiac Arrest and Resuscitation
Rika Bajorat,
Lena Danckert,
Florian Ebert,
Theresa Bancken,
Stefan Bergt,
Felix Klawitter,
Brigitte Vollmar,
Daniel A. Reuter,
Tobias Schürholz,
Johannes Ehler
Affiliations
Rika Bajorat
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Lena Danckert
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Florian Ebert
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Theresa Bancken
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Stefan Bergt
Department of Anesthesiology and Intensive Care Medicine, MEDICLIN Müritz-Klinikum, 17192 Waren, Germany
Felix Klawitter
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Brigitte Vollmar
Institute of Experimental Surgery, Rostock University Medical Center, 18057 Rostock, Germany
Daniel A. Reuter
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
Tobias Schürholz
Department of Intensive and Intermediate Care, University Hospital RWTH Aachen, 52074 Aachen, Germany
Johannes Ehler
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057 Rostock, Germany
The synthetic antimicrobial peptides (sAMPs) Pep19-2.5 and Pep19-4LF have been shown in vitro and in vivo to reduce the release of pro-inflammatory cytokines, leading to the suppression of inflammation and immunomodulation. We hypothesized that intervention with Pep19-2.5 and Pep19-4LF immediately after cardiac arrest and resuscitation (CA-CPR) might attenuate immediate systemic inflammation, survival, and long-term outcomes in a standardized mouse model of CA-CPR. Long-term outcomes up to 28 days were assessed between a control group (saline) and two peptide intervention groups. Primarily, survival as well as neurological and cognitive parameters were assessed. In addition, systemic inflammatory molecules and specific biomarkers were analyzed in plasma as well as in brain tissue. Treatment with sAMPs did not provide any short- or long-term benefits for either survival or neurological outcomes, and no significant benefit on inflammation in the CA-CPR animal model. While no difference was found in the plasma analysis of early cytokines between the intervention groups four hours after resuscitation, a significant increase in UCH-L1, a biomarker of neuronal damage and blood–brain barrier rupture, was measured in the Pep19-4LF-treated group. The theoretical benefit of both sAMPs tested here for the treatment of post-cardiac arrest syndrome could not be proven.
