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Introduction: Therapeutic hypothermia (TH) can improve neurological outcome after cardiac arrest (CA); little is known about how cooling actually affects brain dynamics after resuscitation from CA. Hypothesis: The aim of this study was to investigate the effects of TH on brain microcirculation and metabolism after CA. Methods: 10 anesthetized, invasively monitored and mechanically ventilated domestic pigs were randomized into two groups (n=5): normothermia (NT, 39.5 ± 1.0 °C) and therapeutic hypothermia (TH, 34.0 ± 1.0°C). After 3 min of untreated ventricular fibrillation, cardiopulmonary resuscitation (CPR) was started and continued for 3 min before defibrillation. Hypothermia was induced at the start of CPR using IV infusion of 30 mL/kg cold saline for 60 min, trans-nasal evaporative cooling (Rhinochill, Benechill Inc, USA) and surface cooling with ice packs. Cooling was maintained for 6 hours, followed by controlled rewarming to baseline temperature. Intraparenchymal probes were used to measure brain temperature (Licox CC1.SB, Integra, NeuroSciences Ltd., Hamphsire, UK) and the lactate-pyruvate ratio (LPR, microdialysis CMA20, CMA, Sweden) hourly. After left craniectomy, the microvascular network of the frontal cortex was evaluated using Sidestream Dark-Field videomicroscopy (Microscan, MicroVision Medical, Netherlands) at baseline (T0), 1 hour after cooling induction (T1), at the end of hypothermia (T2) and after rewarming (T3). The proportion of perfused cerebral small vessels (PPV) was calculated using standard formulas. Results: Time to return of spontaneous circulation was similar in both groups (7 [6-22] mins for NT and 9 [6-21] mins for TH). Microvascular perfusion was significantly decreased after CA, but was better preserved in the TH than in the NT group (PPV: T0 87 ± 3 vs 86 ± 2, T1 37 ± 13 vs 29 ± 3, T2 36 ± 15 vs 24 ± 7, T3 58 ± 7 vs 17 ± 3 – p<0.01). The LPR was higher in the NT than in the TH group throughout the study period (T0 14.1 ± 3.6 vs 13.4 ± 2.6, T1 27.4 ± 9.7 vs 21.7 ± 4.4, T2 43.7 ± 20.4 vs 35.4 ± 9.4, T3 110.4 ± 57.3 vs 62.8 ± 12.6, p<0.05). Conclusions: The cerebral microcirculation was significantly altered after resuscitated CA; TH attenuated these microvascular alterations and had a protective effect on brain metabolism.