TY - JOUR
T1 - Ventilation With Argon Improves Survival With Good Neurological Recovery After Prolonged Untreated Cardiac Arrest in Pigs
AU - Fumagalli, Francesca
AU - Olivari, Davide
AU - Boccardo, Antonio
AU - De Giorgio, Daria
AU - Affatato, Roberta
AU - Ceriani, Sabina
AU - Bariselli, Simone
AU - Sala, Giulia
AU - Cucino, Alberto
AU - Zani, Davide
AU - Novelli, Deborah
AU - Babini, Giovanni
AU - Magliocca, Aurora
AU - Russo, Ilaria
AU - Staszewsky, Lidia
AU - Salio, Monica
AU - Lucchetti, Jacopo
AU - Maisano, Antonio Marco
AU - Fiordaliso, Fabio
AU - Furlan, Roberto
AU - Gobbi, Marco
AU - Luini, Mario Vittorio
AU - Pravettoni, Davide
AU - Scanziani, Eugenio
AU - Belloli, Angelo
AU - Latini, Roberto
AU - Ristagno, Giuseppe
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/12/15
Y1 - 2020/12/15
N2 - 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%.
AB - 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%.
KW - argon
KW - cardiac arrest
KW - neurological outcome
KW - noble gas
KW - treatment
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U2 - 10.1161/JAHA.120.016494
DO - 10.1161/JAHA.120.016494
M3 - Article
C2 - 33289464
AN - SCOPUS:85098531699
VL - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 24
M1 - e016494
ER -