Therapeutic hypothermia promotes cerebral blood flow recovery and brain homeostasis after resuscitation from cardiac arrest in a rat model

Abstract

Laboratory and clinical studies have demonstrated that therapeutic hypothermia (TH), when applied as soon as possible after resuscitation from cardiac arrest (CA), results in better neurological outcome. This study tested the hypothesis that TH would promote cerebral blood flow (CBF) restoration and its maintenance after return of spontaneous circulation (ROSC) from CA. Twelve Wistar rats resuscitated from 7-min asphyxial CA were randomized into two groups: hypothermia group (7 H, n = 6), treated with mild TH (33-34℃) immediately after ROSC and normothermia group (7 N, n = 6,37.0 ± 0.5℃). Multiple parameters including mean arterial pressure, CBF, electroencephalogram (EEG) were recorded. The neurological outcomes were evaluated using electrophysiological (information quantity, IQ, of EEG) methods and a comprehensive behavior examination (neurological deficit score, NDS). TH consistently promoted better CBF restoration approaching the baseline levels in the 7 H group as compared with the 7 N group. CBF during the first 5-30 min post ROSC of the two groups was 7 H:90.5% ± 3.4% versus 7 N:76.7% ± 3.5% (P < 0.01). Subjects in the 7 H group showed significantly better IQ scores after ROSC and better NDS scores at 4 and 24 h. Early application of TH facilitates restoration of CBF back to baseline levels after CA, which in turn results in the restoration of brain electrical activity and improved neurological outcome.

Keywords: Cardiac arrest; cerebral blood flow; laser speckle contrast imaging; mean arterial pressure; therapeutic hypothermia.

Figure 1.

(a) Schematic diagram of LSCI experimental setup. (b) Representative LSCI image during the CA. ROI: region of interest. (c) Schematic diagram of CA experimental procedure. TH was applied immediately after ROSC. (d) Representative LSCI images of selected ROI at difference stage of CA and CBF values in two groups (Hypothermia, 7 H and Normothermia, 7 N). CA: cardiac arrest; CPR; cardiopulmonary resuscitation; ROSC: return of spontaneous circulation. The double black asterisk (**) represents statistical significance with P < 0.01.

Figure 2.

TH was applied immediately after ROSC. Temperature recording of hypothermia (7 H) and normothermia (7 N) post ROSC period. The solid line is temperature in 7 H and the dotted line is of 7 N. Target temperature (33–34℃) was achieved at 5-min post ROSC. Temperature was significantly different (**P < 0.01) between the two groups afterwards (5–120 min post ROSC).

Figure 3.

(a) NDS in hypothermia (7 H) and normothermia (7 N) group at baseline (BL); asphyxia (ASP); 4 h post ROSC (4 H) and 24 h post ROSC (24 H). The NDS was significantly different between the two groups at 4 H and 24 H post ROSC. (b) Comparison of information quantity (IQ) of EEG data for two groups (hypothermia, 7 H and normothermia, 7 N) post ROSC. There was a significant difference during post ROSC between the two groups. The black asterisk (*) represents statistical significance with P < 0.05; the double black asterisk (**) represents statistical significance with P < 0.01.

Figure 4.

(a) Change of CBF (percent of baseline) in the post ROSC in two groups (hypothermia, 7 H and normothermia, 7 N); (b) Change in MAP post ROSC in two groups (hypothermia, 7 H and normothermia, 7 N). The black asterisk (*) represents statistical significance with P < 0.05; the double black asterisk (**) represents statistical significance with P < 0.01.

Figure 5.

Representative recording of CBF, EEG and MAP post ROSC. This period was divided by three blocks per the EEG activities: Non-DCA: non-detectable cortical activity); ICA: intermittent cortical activity; CCA: continuous cortical activity; APU: arbitrary perfusion units). (a) Temperature in two groups (7 H vs. 7 N) at three blocks; (b) Information quantity (IQ) in two groups (7 H vs. 7 N) at three blocks; (c) Mean arterial pressure (MAP) in two groups (7 H vs. 7 N) at three blocks; (d) Cerebral blood flow (CBF) in two groups (7 H vs. 7 N) at three blocks. 7 H, no fill bar; 7 N diagonal pattern fill bar. The black asterisk (*) represents statistical significance with P < 0.05. The black double asterisk (**) represents statistical significance with P < 0.01).