Effect of different therapeutic time windows of mild hypothermia on neurological protection from ventricular fibrillation in rabbit models

Abstract

Objective To investigate the effects of mild hypothermia on post-resuscitation neurological outcome after ventricular fibrillation (VF) in rabbits. Methods Forty-five adult New Zealand rabbits were induced VF by direct current of electricity. The rabbits were randomly(random number) divided into following groups: normothermic resuscitation group (NR), mild hypothermia pre-arrest group (HP), mild hypothermia resuscitation 30 min group (HRe30), mild hypothermia resuscitation 90 min group (HRe90), normothermic sham group (NS), and hypothermia sham group (HS). The rabbits of NR group were observed for 600 min in room temperature after restoration of spontaneous circulation (ROSC). The mild hypothermia was induced by surface cooling, and maintained for 600 min after the aimed low temperature reached. The arterial blood samples were collected for determining neuron-specific enolase (NSE) and thioredoxin (Trx) and the mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure raise and fall rate (±dp/dtmax) were observed at 15 min before CA, and 30 min, 60 min, 120 min, 360 min and 600 min after ROSC. After the animals were sacrificed at 600 min after ROSC, the whole brain of animals was harvested and observed under light microscope to calculate the apoptotic index of the hippocampal CA1 neurons by using TUNEL method. One-way ANOVA was used to determine the statistical significance between two groups, a two-tailed value of P<0.05 was considered statistically significant. Results (1) Hemodynamically compared with normal temperature groups, HR was lower in hypothermia groups. Compared with NR, HRe30, and HRe90 group, LVEDP was higher in HP group at 30 min after ROSC(3.4±0.8 vs. 4.6±1.0, 4.1±0.5, 4.3±0.2, F=9.85, P=0.019).In HP group, the level of +dp/dtmax was higher than that in NR, HRe30 and HRe90 groups at 30 min and 120 min after ROSC. In HP group, the level of -dp/dtmax was higher than that of NR group at 30 min, 60 min, 120 min, 360 min and 600 min after ROSC. (2) Serologically compared with HP, HRe30 and HRe90 group, NSE levels were higher in NR group at 60 min,120 min and 360 min after ROSC. Compared with NR, HRe30, and HRe90 group, Trx levels in NR group were lower at 60 min,120 min, 360 min and 600 min after ROSC. Compared with HP group, Trx levels in HRe30 and HRe90 groups were higher at 60 min,120 min, 360 min and 600 min after ROSC. (3) Pathologically compared with NR group, histopathological changes in hippocampus CA1 area were milder found in HP, HRe30 and HRe90 groups. AI (%) was lower in HP, HRe30 and HRe90 groups than that in NR group[(62.25±10.43)% vs. (20.61±5.02)%, (25.08±3.92)%, (30.33±7.15)%, P=0.001]. Concusions This study shows that hypothermia should be initiated as soon as possible, and especially early intra-arrest cooling appears to be significantly better than post-ROSC cooling and normothermia. Key words: Post-cardiac arrest syndrome; Mild therapeutic hypothermia; Ventricular fibrillation; Thioredoxin; Neurological protection; Rabbit