Matthias Kohlhauer1, Fanny Lidouren, Isabelle Remy-Jouet, Nicolas Mongardon, Clovis Adam, Patrick Bruneval, Hakim Hocini, Yves Levy, Fabiola Blengio, Pierre Carli, Benoit Vivien, Jean-Damien Ricard, Philippe Micheau, Hervé Walti, Mathieu Nadeau, Raymond Robert, Vincent Richard, Paul Mulder, David Maresca, Charlie Demené, Mathieu Pernot, Mickael Tanter, Bijan Ghaleh, Alain Berdeaux, Renaud Tissier. 1. 1Inserm, U955, Equipe 03, Créteil, France. 2Université Paris Est, UMR_S955, DHU A-TVB, UPEC, Créteil, France. 3Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France. 4Inserm, U1096, Rouen, France. 5Assistance Publique, Hôpitaux de Paris, Hôpital du Kremlin-Bicêtre, Service d'Anatomie Pathologique, Le Kremlin-Bicêtre, France. 6Inserm, U970, Paris, France. 7Inserm, U955, Equipe 16, Créteil, France. 8Vaccine Research Institute, Créteil, France. 9SAMU de Paris, Département d'Anesthésie Réanimation, Hôpital Universitaire Necker-Enfants Malades, Université Paris Descartes-Paris V, Paris, France. 10Inserm, IAME, 1137, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France. 11Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-chirurgicale, Colombes, France. 12Department of Mechanical Engineering, University of Sherbrooke, QC, Canada. 13Department of Physiology, University of Sherbrooke, QC, Canada. 14Institut Langevin, CNRS UMR 7587, INSERM U979, ESPCI ParisTech, Paris, France.
Abstract
OBJECTIVES: Total liquid ventilation provides ultrafast and potently neuro- and cardioprotective cooling after shockable cardiac arrest and myocardial infarction in animals. Our goal was to decipher the effect of hypothermic total liquid ventilation on the systemic and cerebral response to asphyxial cardiac arrest using an original pressure- and volume-controlled ventilation strategy in rabbits. DESIGN: Randomized animal study. SETTING: Academic research laboratory. SUBJECTS: New Zealand Rabbits. INTERVENTIONS: Thirty-six rabbits were submitted to 13 minutes of asphyxia, leading to cardiac arrest. After resumption of spontaneous circulation, they underwent either normothermic life support (control group, n = 12) or hypothermia induced by either 30 minutes of total liquid ventilation (total liquid ventilation group, n = 12) or IV cold saline (conventional cooling group, n = 12). MEASUREMENTS AND MAIN RESULTS: Ultrafast cooling with total liquid ventilation (32 °C within 5 min in the esophagus) dramatically attenuated the post-cardiac arrest syndrome regarding survival, neurologic dysfunction, and histologic lesions (brain, heart, kidneys, liver, and lungs). Final survival rate achieved 58% versus 0% and 8% in total liquid ventilation, control, and conventional cooling groups (p < 0.05), respectively. This was accompanied by an early preservation of the blood-brain barrier integrity and cerebral hemodynamics as well as reduction in the immediate reactive oxygen species production in the brain, heart, and kidneys after cardiac arrest. Later on, total liquid ventilation also mitigated the systemic inflammatory response through alteration of monocyte chemoattractant protein-1, interleukin-1β, and interleukin-8 transcripts levels compared with control. In the conventional cooling group, cooling was achieved more slowly (32 °C within 90-120 min in the esophagus), providing none of the above-mentioned systemic or organ protection. CONCLUSIONS: Ultrafast cooling by total liquid ventilation limits the post-cardiac arrest syndrome after asphyxial cardiac arrest in rabbits. This protection involves an early limitation in reactive oxidative species production, blood-brain barrier disruption, and delayed preservation against the systemic inflammatory response.
OBJECTIVES: Total liquid ventilation provides ultrafast and potently neuro- and cardioprotective cooling after shockable cardiac arrest and myocardial infarction in animals. Our goal was to decipher the effect of hypothermic total liquid ventilation on the systemic and cerebral response to asphyxial cardiac arrest using an original pressure- and volume-controlled ventilation strategy in rabbits. DESIGN: Randomized animal study. SETTING: Academic research laboratory. SUBJECTS:New Zealand Rabbits. INTERVENTIONS: Thirty-six rabbits were submitted to 13 minutes of asphyxia, leading to cardiac arrest. After resumption of spontaneous circulation, they underwent either normothermic life support (control group, n = 12) or hypothermia induced by either 30 minutes of total liquid ventilation (total liquid ventilation group, n = 12) or IV cold saline (conventional cooling group, n = 12). MEASUREMENTS AND MAIN RESULTS: Ultrafast cooling with total liquid ventilation (32 °C within 5 min in the esophagus) dramatically attenuated the post-cardiac arrest syndrome regarding survival, neurologic dysfunction, and histologic lesions (brain, heart, kidneys, liver, and lungs). Final survival rate achieved 58% versus 0% and 8% in total liquid ventilation, control, and conventional cooling groups (p < 0.05), respectively. This was accompanied by an early preservation of the blood-brain barrier integrity and cerebral hemodynamics as well as reduction in the immediate reactive oxygen species production in the brain, heart, and kidneys after cardiac arrest. Later on, total liquid ventilation also mitigated the systemic inflammatory response through alteration of monocyte chemoattractant protein-1, interleukin-1β, and interleukin-8 transcripts levels compared with control. In the conventional cooling group, cooling was achieved more slowly (32 °C within 90-120 min in the esophagus), providing none of the above-mentioned systemic or organ protection. CONCLUSIONS: Ultrafast cooling by total liquid ventilation limits the post-cardiac arrest syndrome after asphyxial cardiac arrest in rabbits. This protection involves an early limitation in reactive oxidative species production, blood-brain barrier disruption, and delayed preservation against the systemic inflammatory response.
Authors: M Kohlhauer; V R Pell; N Burger; A M Spiroski; A Gruszczyk; J F Mulvey; Amin Mottahedin; A S H Costa; C Frezza; B Ghaleh; M P Murphy; R Tissier; T Krieg Journal: Basic Res Cardiol Date: 2019-03-15 Impact factor: 17.165