Postresuscitation Treatment With Argon Improves Early Neurological Recovery in a Porcine Model of Cardiac Arrest

Ristagno, Giuseppe; Fumagalli, Francesca; Russo, Ilaria; Tantillo, Simona; Zani, Davide Danilo; Locatelli, V.; Maglie, Marcella De; Novelli, Deborah; Staszewsky, Lidia; Vago, Tarcisio; Belloli, A.; Giancamillo, M. Di; Fries, Michael; Masson, Serge; Scanziani, Eugenio; Latini, Roberto

doi:10.1097/shk.0000000000000049

Cited by 52 publications

(90 citation statements)

References 25 publications

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“…This creates an ideal substrate for arrhythmias by causing heterogeneities in terms of excitability, refractory period and conduction [46]. The inconvenient is that it is difficult to predict the time and rate of VF occurrence [48][49][50].…”

Section: Myocardial Ischemia-induced Ventricular Fibrillationmentioning

confidence: 99%

“…In survivors, neurological function is typically assessed using clinical deficit scores with specific grids for each species. They are based on the clinical evaluation of consciousness, behavior, breathing, reflexes, and locomotion tests [9,[11][12][13][28][29][30][31]41,50,53]. Neurological recovery can be further assessed with quantitative behavioral tests in rodents, such as the T maze or the Morris maze test [59][60][61].…”

Section: Neurological Function and Survivalmentioning

confidence: 99%

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How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

Blondel¹,

Kohlhauer²,

Zilberstein³

et al. 2016

JDVAR

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Animal research is essential to propose new therapeutic approaches limiting the sequels of cardiac arrest in human and veterinary medicine. The ultimate goal is to improve the long term prognosis and neurological recovery. For such investigations, the use of animal models seems unavoidable as cardiac arrest provokes multiple visceral consequences as well as inflammatory response and coagulopathy. These models allow not only a better understanding of the pathophysiology but also the investigation of new treatment strategies to improve basic life support efficiency or prevent multi-organ failure. In this review, we are summarizing the characteristics of the main animal models used in resuscitation sciences. The choice of the species and methods of evaluation of cardiac arrest is crucial. These studies often concern human medicine but they can also address fundamental questions for veterinary research as they are mostly based on animal research.

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Section: Myocardial Ischemia-induced Ventricular Fibrillationmentioning

confidence: 99%

Section: Neurological Function and Survivalmentioning

confidence: 99%

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

Blondel¹,

Kohlhauer²,

Zilberstein³

et al. 2016

JDVAR

View full text Add to dashboard Cite

show abstract

“…The argon exposure protocols were defined empirically based on previous reports. Argon concentrations of 30-70% applied for 45-180 min had shown protective effects in previous studies [7,19]. The boxes were placed into an incubator and warmed to 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Rodent models of cardiac arrest followed by cardiopulmonary resuscitation have exhibited improved neurological performance and decreased neuronal damage with argon postconditioning [7,8,9]. Argon postconditioning was also neuroprotective in stroke models (middle cerebral artery occlusion) [10,11] and in vitro models of cerebral ischaemia and traumatic brain injury [12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress

Hafner

Soto-Gonzalez

et al. 2016

Eur Surg Res

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Background: Oxidative stress is the predominant pathogenic mechanism of ischaemia-reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H₂O₂) to induce oxidative stress. Methods: A549 airway epithelial cells were treated with a cytotoxic concentration of H₂O₂ after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence-activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways. Results: Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H₂O₂-induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min. Conclusions: Argon preconditioning protects airway epithelial cells from H₂O₂-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs.

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“…They are based on the clinical evaluation of consciousness, behavior, breathing, reflexes, and locomotion tests. 9,[11][12][13][28][29][30][31]41,50,53 Neurological recovery can be further assessed with quantitative behavioral tests in rodents, such as the T maze or the Morris maze test. [59][60][61] In addition to the clinical evaluation of neurological function, histopathological damages are also usually evaluated in most experimental studies.…”

Section: Main End-points For Cardiac Arrest Studies In Animals Neurolmentioning

confidence: 99%

Untitled

2016

JDVAR

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Abbreviations: CPR, cardiopulmonary resuscitation; ROSC, resumption of spontenaeous circulation; VF, ventricular fibrillation IntroductionCardiac arrest is an important public health issue in humans in industrialized countries with, e.g., 35,000 to 40,000 new cases each year in France.1,2 Despite increasing implementation of cardiopulmonary resuscitation (CPR) in the field, resumption of spontaneous circulation (ROSC) is typically obtained in less than 35% of these patients. Resuscitated victims often present a post cardiac arrest syndrome with a complex physiopathology combining hemodynamic failure, neurological dysfunction and multi-visceral injury, leading to an additional worsening of the prognosis. Ultimately, less than 8% of the patients survive with favorable neurological function at hospital discharge. [3][4][5] In this context, experimental research is crucial to provide new therapeutic approaches increasing CPR efficiency and initial resuscitation, as well as long term prognosis and neurological recovery. For such investigations, the use of animal models seems unavoidable as cardiac arrest provokes multiple visceral consequences as well as inflammatory response and coagulopathy. These models allow not only a better understanding of the pathophysiology but also the investigation of new treatment strategies to improve CPR efficiency or prevent multi-organ failure. This field of research can also address fundamental questions for veterinary research, beyond the relevance for human medicine. Impact of species-differencesIn general, animal models of cardiac arrest are using rodents, rabbits, pigs or dogs. All these species present anatomical or physiological specificities that should been considered in the design of the study, depending upon the specific goals and corresponding end-points. Cardiac arrest in rodentsAs usual in biomedical research, rodents are widely used in resuscitation sciences due to their relative ease of manipulation, low cost and extensive possibilities of mechanistic investigations with genetically modified animals. Obviously, this use is associated with several limitations related to their cardiovascular anatomy and physiology. On the one hand, rodents present two different cranial venae cavae (right and left) with a coronary sinus formed by the proximal part of the left cranial vena cava.6 This directly modifies the coronary perfusion during cardiac massage through different venous return as compared to large animals.7 In addition, due to their very low body mass, cardiac massage could make blood circulating through direct heart compression, while it is mostly acting through thoracic pumping in large animals. On the other hand, spontaneous heart rate is much higher in rodents than in large animals and humans as usual values average 260-450 or 500-600 beats per minute in awake rats and mice, respectively. 7,8 This directly impacts the required chest compression rate in those species as mice should undergo ≈400 compressions per min to be resuscitated. [9][10][11][12][13][14] Magnetic ...

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Postresuscitation Treatment With Argon Improves Early Neurological Recovery in a Porcine Model of Cardiac Arrest

Abstract: In this model, postresuscitation treatment with argon allowed for a faster and complete neurologic recovery, without detrimental effects on hemodynamics and respiratory gas exchanges.

Cited by 52 publications

References 25 publications

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress

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