title: A Brief Period of Hypothermia Induced by Total Liquid Ventilation Decreases End-Organ Damage and Multiorgan Failure Induced by Aortic Cross-Clamping.
abstract: In animal models, whole-body cooling reduces end-organ injury after cardiac arrest and other hypoperfusion states. The benefits of cooling in humans, however, are uncertain, possibly because detrimental effects of prolonged cooling may offset any potential benefit. Total liquid ventilation (TLV) provides both ultrafast cooling and rewarming. In previous reports, ultrafast cooling with TLV potently reduced neurological injury after experimental cardiac arrest in animals. We hypothesized that a brief period of rapid cooling and rewarming via TLV could also mitigate multiorgan failure (MOF) after ischemia-reperfusion induced by aortic cross-clamping.
  
  
  
  Anesthetized rabbits were submitted to 30 minutes of supraceliac aortic cross-clamping followed by 300 minutes of reperfusion. They were allocated either to a normothermic procedure with conventional ventilation (control group) or to hypothermic TLV (33°C) before, during, and after cross-clamping (pre-clamp, per-clamp, and post-clamp groups, respectively). In all TLV groups, hypothermia was maintained for 75 minutes and switched to a rewarming mode before resumption to conventional mechanical ventilation. End points included cardiovascular, renal, liver, and inflammatory parameters measured 300 minutes after reperfusion.
  
  
  
  In the normothermic (control) group, ischemia-reperfusion injury produced evidence of MOF including severe vasoplegia, low cardiac output, acute kidney injury, and liver failure. In the TLV group, we observed gradual improvements in cardiac output in post-clamp, per-clamp, and pre-clamp groups versus control (53 ± 8, 64 ± 12, and 90 ± 24 vs 36 ± 23 mL/min/kg after 300 minutes of reperfusion, respectively). Liver biomarker levels were also lower in pre-clamp and per-clamp groups versus control. However, acute kidney injury was prevented in pre-clamp, and to a limited extent in per-clamp groups, but not in the post-clamp group. For instance, creatinine clearance was 4.8 ± 3.1 and 0.5 ± 0.6 mL/kg/min at the end of the follow-up in pre-clamp versus control animals (P = .0004). Histological examinations of the heart, kidney, liver, and jejunum in TLV and control groups also demonstrated reduced injury with TLV.
  
  
  
  A brief period of ultrafast cooling with TLV followed by rapid rewarming attenuated biochemical and histological markers of MOF after aortic cross-clamping. Cardiovascular and liver dysfunctions were limited by a brief period of hypothermic TLV, even when started after reperfusion. Conversely, acute kidney injury was limited only when hypothermia was started before reperfusion. Further work is needed to determine the clinical significance of our results and to identify the optimal duration and timing of TLV-induced hypothermia for end-organ protection in hypoperfusion states.
authors.affiliation: From the *Inserm, U955, Equipe 3, Créteil, France; †Université Paris Est, UMR_S 955, UPEC, DHU A-TVB, Créteil, France; ‡Université Paris Est, Ecole Nationale Vétérinaire Alfort, Maisons Alfort, France; §Service d' Anesthésie et des Réanimations Chirurgicales, DHU A-TVB, Hôpitaux Universitaires Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France; ‖Inserm, U1082, Poitiers, France; ¶Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France; #CHU de Poitiers, Service de Biochimie, Poitiers, France; **Inserm, UMR 970, Paris Cardiovascular Research Center, Paris, France; ††Université de Sherbrooke, Sherbrooke, Canada; and ‡‡Service de Réanimation Médicale, Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mongardon
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohlhauer
authors.forename: Fanny
authors.initials: F
authors.lastname: Lidouren
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
authors.forename: Sébastien
authors.initials: S
authors.lastname: Giraud
authors.forename: Alice
authors.initials: A
authors.lastname: Hutin
authors.forename: Bruno
authors.initials: B
authors.lastname: Costes
authors.forename: Caroline
authors.initials: C
authors.lastname: Barau
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Philippe
authors.initials: P
authors.lastname: Micheau
authors.forename: Alain
authors.initials: A
authors.lastname: Cariou
authors.forename: Gilles
authors.initials: G
authors.lastname: Dhonneur
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Renaud
authors.initials: R
authors.lastname: Tissier
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D003250:Constriction; D007036:Hypothermia, Induced / Q000379:methods*; D021061:Liquid Ventilation / Q000379:methods*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D011817:Rabbits; D011897:Random Allocation; D013997:Time Factors