Neuroprotective effect of Shenfu Injection () following cardiac arrest in pig correlates with improved mitochondrial function and cerebral glucose uptake.

ABSTRACT

OBJECTIVE: To test whether Shenfu Injection (, SFI) might attenuate the impact of cerebral energy dysfunction after resuscitation in a pig model of cardiac arrest (CA). METHODS: Thirty-four Wuzhishan miniature inbred pigs were randomly divided into three groups the SFI group (n=12), the saline group (SA group, n=12), and the sham-operated group (sham group, n=10). Following successful return of spontaneous circulation (ROSC) from 8-min untreated ventricular fibrillation, animals received a continuous infusion of either SFI (0.2 mL/min) or saline for 6 h. Cerebral performance category score was evaluated at 24 and 48 h after ROSC, followed by positron emission tomography and computed tomography scans of cerebral glucose uptake. Surviving pigs were euthanized 48 h after ROSC, and the brains were removed for detecting mitochondrial function. RESULTS: Compared with the SA group, SFI treatment produced a better neurologic outcome 48 h after ROSC (P<0.05). However, there was no significant difference of survival rate between the SA and SFI groups (83.3% vs. 81.8%, P>0.05). After ROSC, the SA group showed a decrease in the maximum standardized uptake value of different regions in the brain tissue, where SFI treatment can ameliorate these decreases (P<0.01 or P<0.05). Improved mitochondrial respiratory properties and higher mitochondrial membrane potential were also found following SFI treatment compared with the SA group at 48 h after ROSC (P<0.05 or P<0.01). CONCLUSION: SFI treatment after resuscitation has significant neuroprotective effects against disruption of cerebral energy metabolism from CA by improving glucose uptake and by normalizing mitochondrial function.