Association between early post-resuscitation heart rate and survival with neurological recovery in a pig model of cardiac arrest Daria De Giorgio, Francesca Fumagalli, Aurora Magliocca, Giulia Merigo, Marianna Cerrato, Carlo Perego, Giuseppe Ristagno Resuscitation Plus, 2026 Objective: Heart rate (HR), a readily available clinical parameter, has proven prognostic value in cardiovascular disease and may provide similar insights following cardiac arrest. This study investigated whether post-resuscitation HR might predict functional recovery in a preclinical porcine model of cardiac arrest and cardiopulmonary resuscitation (CPR). Methods: Retrospective analyses were conducted in data from earlier prospective animal studies. Ninety-six pigs successfully resuscitated after 8-12 min of ischemically induced ventricular fibrillation, followed by 5 min of CPR prior to defibrillation attempt, were included in the study. HR, arterial and central venous pressures were continuously monitored for 4 h after resuscitation. Survival with neurological function was assessed up to 96 h post-resuscitation by the optimal performance category (OPC) score, with 1-2 considered as good outcome and 3-5 as poor outcome. Results: < 0.01). Lower HR, shorter no-flow and low-flow durations, higher diastolic, mean, and coronary perfusion pressures were associated with good outcome. However, only HR was an independent predictor of good neurological recovery (OR 0.971 [0.947-0.995] per 1 bpm increase); a HR > 135 bpm predicted poor outcome with 80% sensitivity and 70% specificity. Conclusions: In this model, lower post-resuscitation HR was independently associated with survival with favorable neurological recovery.
Association between early arterial pH, base excess and lactate and 24-h mortality and neurological outcomes after cardiac arrest and cardiopulmonary resuscitation: a translational study Francesca Callegari, Daria De Giorgio, Giulia Merigo, Marianna Cerrato, Ornella Tinelli, Aurora Magliocca, Elisa R. Zanier, Giuseppe Ristagno, Francesca Fumagalli Resuscitation Plus, 2026 Aim: We aimed to assess the translational relevance of blood gas-derived acid-base parameters measured in rat and pig models of cardiac arrest and cardiopulmonary resuscitation, evaluating their potential as predictors of mortality and poor neurological outcome. Methods: Blood gas analyses were performed 4 h after return of spontaneous circulation. Neurological recovery was assessed using Neurological Deficit Score in rats, overall performance category in pigs, and cerebral performance category in patients. Nonlinear associations between blood gas-derived acid-base parameters and outcomes were analyzed using a generalized additive model. Receiver operating characteristics curve analyses were performed. Results: In a multivariate regression analysis area under the curve, considering pH, base excess and lactate, for prediction of mortality were respectively: 0.796 (95%CI: 0.635-0.956), 0.980 (95%CI: 0.946-1.000), 0.959 (95%CI: 0.896-1.000) in rats; 0.908 (95%CI: 0.826-0.990), 0.933 (95%CI: 0.863-1.000), 0.798 (95%CI: 0.588-1.000) in pigs; and 0.830 (95%CI: 0.724-0.936), 0.832 (95%CI: 0.731-0.933), 0.839 (95%CI: 0.738-0.940) in patients. Area under the curve, considering pH, base excess and lactate, for prediction of poor neurological outcome were respectively: 0.673 (95%CI: 0.515-0.831), 0.724 (95%CI: 0.576-0.872), 0.900 (95%CI: 0.760-1.000) in pigs; and 0.835 (95%CI: 0.734-0.937), 0.835 (95%CI: 0.735-0.936), 0.884 (95%CI: 0.793-0.945) in patients. Conclusion: Arterial pH, base excess and lactate were early independent predictors of both 24-h mortality and neurological outcome following cardiac arrest in animal models and in humans. BE showed the highest predictive value for mortality, while lactate was the strongest predictor for poor neurological outcome.
Impact of obesity on myocardial function and survival after cardiac arrest and cardiopulmonary resuscitation in a rat model Marianna Cerrato, Daria De Giorgio, Aurora Magliocca, Elisa Roncati Zanier, Giuseppe Ristagno, Francesca Fumagalli Scientific Reports, 2025 Obesity is a recognized risk factor for cardiovascular morbidity and mortality, however its impact on survival following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remains controversial. Therefore, the aim of this study was to evaluate the feasibility of a preclinical model of CA/CPR in obese rats as well as 72-hour (h) survival, and investigate the effect of obesity on myocardial dysfunction post-CA/CPR. Rats were subjected to 6 min of untreated ventricular fibrillation and to 6 min of CPR. Hemodynamic parameters were continuously recorded up to 4 h, serial blood samples were collected and echocardiography was performed at 2 and 4 h after resuscitation. Rats were sacrificed 72 and 4 h after resuscitation. After CA, no obese rats survived up to 72 h compared to controls whereas each rat developed marked post- return of spontaneous circulation hemodynamic impairment during the 4 h observation; obese rats showed an impairment in diastolic function as well as a significant increase in troponin T plasma concentration compared to controls. This could support that obesity negatively impacts survival, hemodynamic stability and left ventricular function after CA.
Detecting pneumothorax during cardiopulmonary resuscitation: The potential of defibrillator measured transthoracic impedance Aurora Magliocca, Donatella De Zani, Giulia Merigo, Marianna Cerrato, Daria De Giorgio, Francesca Motta, Francesca Fumagalli, Davide Zani, Giacomo Grasselli, Giuseppe Ristagno Resuscitation Plus, 2024 Introduction: Pneumothorax is a potentially life-treating condition that can represents a complication of cardiopulmonary resuscitation (CPR). An increase in the total amount of air within the thorax may act as an insulator increasing transthoracic impedance (TTI). The aim of this study was to evaluate the effects of pneumothorax on TTI and on resuscitation success in a swine model of cardiac arrest (CA) and CPR. Methods: Forty pigs undergoing CA and prolonged CPR, and with a chest CT scan performed after resuscitation were included in the study. Pneumothorax was classified as mild, moderate, or severe whether the space occupied by the gas was <15 %, 15-50 %, or >50 % of the hemithorax. TTI was measured and recorded by the defibrillator before each defibrillation, and the last one was used for the analyses. Rate of return of spontaneous circulation (ROSC) and survival up to 96 h were assessed. Results: 66 O severe pneumothorax). Rib fractures were present in all animals with mild-moderate and severe pneumothorax, and in 91% of those without. The total number of rib fractures was significantly higher in animals with severe pneumothorax compared to those without pneumothorax. Conclusion: Pneumothorax causes TTI increases which are proportional to the size of the pneumothorax and ultimately reduce resuscitation success. High prevalence of chest skeletal injuries was observed in this study regardless of the presence of pneumothorax with higher amount of rib fractures in animals with severe pneumothorax. TTI measured by defibrillator can be used to detect the presence of pneumothorax during CPR. Future studies should explore this concept of TTI as a diagnostic tool, in order to improve resuscitation outcome in patients with pneumothorax.
A multimodal characterization of cardiopulmonary resuscitation-associated lung edema Aurora Magliocca, Davide Zani, Donatella De Zani, Valentina Castagna, Giulia Merigo, Daria De Giorgio, Francesca Fumagalli, Vanessa Zambelli, Antonio Boccardo, Davide Pravettoni, Giacomo Bellani, Jean Christophe Richard, Giacomo Grasselli, Emanuele Rezoagli, Giuseppe Ristagno Intensive Care Medicine Experimental, 2024 Background Cardiopulmonary resuscitation-associated lung edema (CRALE) is a phenomenon that has been recently reported in both experimental and out-of-hospital cardiac arrest patients. We aimed to explore the respiratory and cardiovascular pathophysiology of CRALE in an experimental model of cardiac arrest undergoing prolonged manual and mechanical chest compression (CC). Oxygen delivery achieved during mechanical or manual CC were also investigated as a secondary aim, to describe CRALE evolution under different hemodynamic supports generated during CPR. Methods Ventricular fibrillation (VF) was induced and left untreated for 5 min prior to begin cardiopulmonary resuscitation (CPR), including CC, ventilation with oxygen, epinephrine administration and defibrillation. Continuous mechanical and manual CC was performed alternating one of the two strategies every 5 min for a total of 25 min. Unsynchronized mechanical ventilation was resumed simultaneously to CC. A lung computed tomography (CT) was performed at baseline and 1 h after return of spontaneous circulation (ROSC) in surviving animals. Partitioned respiratory mechanics, gas exchange, hemodynamics, and oxygen delivery were evaluated during the experimental study at different timepoints. Lung histopathology was performed. Results After 25 min of CPR, a marked decrease of the respiratory system compliance with reduced oxygenation and CO2 elimination were observed in all animals. The worsening of the respiratory system compliance was driven by a significant decrease in lung compliance. The presence of CRALE was confirmed by an increased lung weight and a reduced lung aeration at the lung CT, together with a high lung wet-to-dry ratio and reduced airspace at histology. The average change in esophageal pressure during the 25-min CPR highly correlated with the severity of CRALE, i.e., lung weight increase. Conclusions In this porcine model of cardiac arrest followed by a 25-min interval of CPR with mechanical and manual CC, CRALE was consistently present and was characterized by lung inhomogeneity with alveolar tissue and hemorrhage replacing alveolar airspace. Despite mechanical CPR is associated with a more severe CRALE, the higher cardiac output generated by the mechanical compression ultimately accounted for a greater oxygen delivery. Whether specific ventilation strategies might prevent CRALE while preserving hemodynamics remains to be proved.
Evolution of brain injury and neurological dysfunction after cardiac arrest in the rat – A multimodal and comprehensive model Carlo Perego, Francesca Fumagalli, Francesca Motta, Marianna Cerrato, Edoardo Micotti, Davide Olivari, Daria De Giorgio, Giulia Merigo, Angelo Di Clemente, Alessandra Mandelli, Gianluigi Forloni, Luigi Cervo, Roberto Furlan, Roberto Latini, Robert W Neumar, Giuseppe Ristagno Journal of Cerebral Blood Flow and Metabolism, 2024 Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.
Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect Giulia Merigo, Gaetano Florio, Fabiana Madotto, Aurora Magliocca, Ivan Silvestri, Francesca Fumagalli, Marianna Cerrato, Francesca Motta, Daria De Giorgio, Mauro Panigada, Alberto Zanella, Giacomo Grasselli, Giuseppe Ristagno Ebiomedicine, 2024 BACKGROUND: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. METHODS: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. FINDINGS: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). INTERPRETATION: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. FUNDING: This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.
Brain kynurenine pathway and functional outcome of rats resuscitated from cardiac arrest Jacopo Lucchetti, Francesca Fumagalli, Davide Olivari, Roberta Affatato, Claudia Fracasso, Daria De Giorgio, Carlo Perego, Francesca Motta, Alice Passoni, Lidia Staszewsky, Deborah Novelli, Aurora Magliocca, Silvio Garattini, Roberto Latini, Giuseppe Ristagno, Marco Gobbi Journal of the American Heart Association, 2021
Esmolol during cardiopulmonary resuscitation reduces neurological injury in a porcine model of cardiac arrest Laura Ruggeri, Francesca Nespoli, Giuseppe Ristagno, Francesca Fumagalli, Antonio Boccardo, Davide Olivari, Roberta Affatato, Deborah Novelli, Daria De Giorgio, Pierpaolo Romanelli, Lucia Minoli, Alberto Cucino, Giovanni Babini, Lidia Staszewsky, Davide Zani, Davide Pravettoni, Angelo Belloli, Eugenio Scanziani, Roberto Latini, Aurora Magliocca Scientific Reports, 2021
Cardiopulmonary Resuscitation–associated Lung Edema (CRALE): A translational study Aurora Magliocca, Emanuele Rezoagli, Davide Zani, Martina Manfredi, Daria De Giorgio, Davide Olivari, Francesca Fumagalli, Thomas Langer, Leonello Avalli, Giacomo Grasselli, Roberto Latini, Antonio Pesenti, Giacomo Bellani, Giuseppe Ristagno American Journal of Respiratory and Critical Care Medicine, 2021
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 Furlan, Marco Gobbi, Mario Vittorio Luini, Davide Pravettoni, Eugenio Scanziani, Angelo Belloli, Roberto Latini, Giuseppe Ristagno Journal of the American Heart Association, 2020
