Effect of mild hypothermia on cerebral microcirculation in a murine cardiopulmonary resuscitation model

BACKGROUND: We hypothesized that mild hypothermia may improve brain microcirculation by reducing cerebral microvascular endothelial cells apoptosis, and this effect may be maximized by moving up the initiation of mild hypothermia from after return of spontaneous circulation (ROSC) to the start of cardiopulmonary resuscitation (CPR). METHODS: A total of 35 rats were randomized into the intra-arrest hypothermia group (IAH), post-resuscitation hypothermia group (PRH), normothermia group (NT), or the sham control group. A craniotomy exposed the parietal cortex for visualization of microcirculation. Ventricular fibrillation was electrically induced and untreated for 8 minutes, followed by 8 minutes of precordial compression and mechanical ventilation. Hypothermia (33 ± 0.5°C) in the IAH and PRH group was induced and maintained for 6 hours at the beginning of CPR or after ROSC, respectively. At baseline, 1, 3, and 6 hours, hemodynamic parameters were measured and the pial microcirculations were visualized with a sidestream dark field imaging video microscope. Microvascular flow index and perfused microvessel density (PMD) were calculated. Rats were euthanized, and brain tissues were removed at 3 and 6 hours separately. Expression of Bax, Bcl-2, and Caspase 3 in brain microvascular endothelial cells was examined by Western blot. RESULTS: Microvascular flow index and PMD were significantly reduced after cardiac arrest and resuscitation (all P < 0.05), and the former was largely preserved by hypothermia regardless when the hypothermia treatment was induced (P < 0.05). Bax and Caspase 3 increased and Bcl-2 decreased significantly after resuscitation, and hypothermia treatment reversed the trend partly (all P < 0.05). A moderate correlation was observed between MFI and those proteins (Bcl-2/BAX: 3 hours: r = 0.730, P = 0.002; 6 hours: r = 0.743, P = 0.002). CONCLUSION: Mild hypothermia improves cerebral microcirculatory blood supply, partly by inhibiting endothelial cell apoptosis. Mild hypothermia induced simultaneously with CPR has shown no additional benefit in microcirculation or endothelial cell apoptosis.