Introduction: Post-resuscitation acute kidney injury (AKI) is a major determinant of mortality after cardiac arrest. We hypothesized that therapeutic hypothermia would attenuate AKI by activating the AMPK/Sirt1/p-NF-κB pathway and thereby suppressing inflammation. Methods: Twenty-four adult male Sprague-Dawley rats underwent 8 minutes of asphyxial cardiac arrest followed by standardized cardiopulmonary resuscitation. Five minutes after return of spontaneous circulation, animals were randomized to normothermia group (NT, 37 ± 0.5 °C; n = 12), hypothermia group (HT, 33 ± 0.5 °C; n = 12) for 6 hours. Sham-operated rats (n=5) served as controls. Survival was monitored for 24 hours. Serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase associated lipocalin (NGAL), and cytokines (TNF-α, IL-1β, IL-6) were measured using enzyme-linked immunosorbent assay (ELISA) at baseline and 24 hours post-resuscitation. Renal injury was graded histologically (H BUN 11.67 ± 0.96 vs. 18.34 ± 1.31 mg/dL; NGAL 10.71 ± 1.60 vs. 18.56 ± 1.46 ng/mL; all p < 0.01). Compared with NT, a lower histologic injury score was observed in HT group (1.3 ± 0.4 vs 3.2 ± 0.5; p < 0.05). Compared with NT, decreased pro-inflammatory cytokines were observed in HT (TNF-α 21.42±1.99 vs. 33.24±2.29 pg/ml, IL-1β 45.75±4.72 vs. 75.63±3.94 pg/ml, IL-6 40.75±4.72 vs. 56.63±3.94 pg/ml, all p < 0.01). Compared with NT, phosphorylation of AMPK, Sirt1, and NF-κB p65 were increased 2.8-, 3.9-, and 3.8-fold, respectively, in HT (all p < 0.01). Conclusions: Early post-resuscitation hypothermia mitigated structural and functional renal injury, suppressed systemic inflammation, and improved short-term survival in this rat CPR model. These benefits appear to be mediated, at least in part, through activation of the AMPK/Sirt1/p-NF-κB axis.
He et al. (Sun,) studied this question.