LAUSR

Introduction: Ultra-fast hypothermia through total liquid ventilation (TLV) has been shown to be neuroprotective after cardiac arrest. Hypothesis: The mechanism could involve a modification in brain metabolic substrat. Method: Anesthetized rabbits were instrumented with a carotid flow probe as well as arterial and jugular venous catheters. A microdialysis catether was implanted in the right brain cortex. Animals were then submitted to 10 min of ventricular fibrillation and cardiopulmonary resuscitation. After resumption of spontaneous circulation (ROSC), they were randomly submitted to ultra-fast cooling to 32°C by TLV (TLV group) or normothermic follow-up (Control) during 4h. Cerebral consumption of lactate, glucose and O 2 was calculated using arteriovenous differences in their content times mean carotid blood flow. Results: In Control, cerebral blood flow was significantly and sustainly decreased after ROSC (61±6 vs 101±6 ml/min after 240 min vs baseline), with a further decrease with hypothermia in TLV group (23±2 ml/min after 240 min, p<0.05). As compared to Control, TLV reduced the cerebral consumption of glucose (-69% at 240 min) and O 2 (-73% at 240 min). Importantly, Control animals showed a dramatic but transient cerebral consumption of lactate during the first 120 min after cardiac arrest (e.g. 124±31 mmol/min at 60 min). Concomitantly, this was associated with an increase in pyruvate extracellular stocks in brain (e.g. 57±10 μmol/L at 30 min). In TLV group, hypothermia blunted this initial burst of lactate consumption (e.g. 41±12 mmol/min at 60 min, p<0,05) and led to an accumulation in extracellular lactate ( e.g. 2053±68 vs 1246±278 μmol/L at 60 min, in TLV and Control respectively). This early build-up of lactate was then progressively consumed after 120 min in TLV group, allowing a delayed accumulation in pyruvate extracellular stocks from 120 min until the end of follow-up (103±19 and 17±4 μmol/L of pyruvate at 240 min in TLV vs Control respectively). Conclusion: Ultra-fast hypothermia reduces the cerebral consumption of lactate during the first 120 min after ROSC, allowing a delayed renewal in pyruvate stocks. This could explain the potent benefit of hypothermia during this early therapeutic window of 120 min.