Introduction:
Clinical studies have demonstrated that the initial rapid decrement in regional cerebral oxygen saturation (rSO
2
) level by near-infrared spectroscopy shortly after ROSC was associated with good neurological outcomes.
Aim:
To evaluate whether the timing of rSO
2
decline shortly after ROSC reflects the severity of brain injury in a well-established rat model of CA/CPR.
Methods:
We used a total of 85 Wister SD rats (male, 435.2±3.1 g).To produce variable severities of brain injury, CA was induced by different asphyxial times and resuscitated by finger chest compressions and mechanical ventilation. Survival time was recorded for 72 hours after ROSC. Daily neurofunctional scores (NFS) were evaluated by an investigator blinded to the experiments. Electroencephalography (EEG), immunohistochemistry, plasma IL-6, and the gene expressions of cytokines (IL-1, IL-6, TNF-α, HMGB-1) and mitochondrial fission-related proteins (Dnm1L, Fis1, Mief1) in the brain were also evaluated.
Result:
Animals in the 12-min CA group exhibited a longer time to EEG recovery after CA/CPR compared with the 6-min group (P<.0001), suggesting the longer CA duration induces a delayed brain electrical recovery. Time from ROSC to achieving the initial minimum rSO
2
value (defined as T
nadir
) was significantly prolonged as CA time increased; 15.3 ± 2.3, 32.1 ± 22.1, and 44.0 ± 2.8 min in 6, 9, and 12min CA, respectively (ANOVA: P<.0001). T
nadir
cut-off of 24-min provided the optimal sensitivity and specificity for predicting good neurologic outcomes (NFS≥60%) at 72 hours after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; P<.01). T
nadir
showed a better predictive power for the good neurological outcome compared with plasma IL-6. Immunohistochemistry at 24 hours post-CA revealed that FJB-positive degenerating neurons in cortex, caudoputamen, and hippocampus were conspicuous in animals with T
nadir
>24-min, but not in animals with T
nadir
≤24-min. Animals with T
nadir
>24 tended to have a higher gene expression level of IL-6 in the brain at 2 hours post-ROSC compared to those with T
nadir
≤24. T
nadir
did not show associations with other inflammatory or mitochondrial fission markers.
Conclusion:
T
nadir
can be a novel predictor for a good neurological outcome after CA/CPR.