Ventilation With Argon Improves Survival With Good Neurological Recovery After Prolonged Untreated Cardiac Arrest in Pigs

Francesca Fumagalli, Davide Olivari, Antonio Boccardo, Daria De Giorgio, Roberta Affatato, Sabina Ceriani, Simone Bariselli, Giulia Sala, Alberto Cucino, Davide Zani, Deborah Novelli, Giovanni Babini, Aurora Magliocca, Ilaria Russo, Lidia Staszewsky, Monica Salio, Jacopo Lucchetti, Antonio Marco Maisano, Fabio Fiordaliso, Roberto FurlanMarco Gobbi, Mario Vittorio Luini, Davide Pravettoni, Eugenio Scanziani, Angelo Belloli, Roberto Latini, Giuseppe Ristagno

Research output: Contribution to journalArticlepeer-review

Abstract

Background Ventilation with the noble gas argon (Ar) has shown neuroprotective and cardioprotective properties in different in vitro and in vivo models. Hence, the neuroprotective effects of Ar were investigated in a severe, preclinically relevant porcine model of cardiac arrest. Methods and Results Cardiac arrest was ischemically induced in 36 pigs and left untreated for 12 minutes before starting cardiopulmonary resuscitation. Animals were randomized to 4-hour post-resuscitation ventilation with: 70% nitrogen-30% oxygen (control); 50% Ar-20% nitrogen-30% oxygen (Ar 50%); and 70% Ar-30% oxygen (Ar 70%). Hemodynamic parameters and myocardial function were monitored and serial blood samples taken. Pigs were observed up to 96 hours for survival and neurological recovery. Heart and brain were harvested for histopathology. Ten animals in each group were successfully resuscitated. Ninety-six-hour survival was 60%, 70%, and 90%, for the control, Ar 50%, and Ar 70% groups, respectively. In the Ar 50% and Ar 70% groups, 60% and 80%, respectively, achieved good neurological recovery, in contrast to only 30% in the control group (P<0.0001). Histology showed less neuronal degeneration in the cortex (P<0.05) but not in the hippocampus, and less reactive microglia activation in the hippocampus (P=0.007), after Ar compared with control treatment. A lower increase in circulating biomarkers of brain injury, together with less kynurenine pathway activation (P<0.05), were present in Ar-treated animals compared with controls. Ar 70% pigs also had complete left ventricular function recovery and smaller infarct and cardiac troponin release (P<0.01). Conclusions Post-resuscitation ventilation with Ar significantly improves neurologic recovery and ameliorates brain injury after cardiac arrest with long no-flow duration. Benefits are greater after Ar 70% than Ar 50%.

Original languageEnglish
Article numbere016494
JournalJournal of the American Heart Association
Volume9
Issue number24
DOIs
Publication statusPublished - Dec 15 2020

Keywords

  • argon
  • cardiac arrest
  • neurological outcome
  • noble gas
  • treatment

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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