Neonatology Fellow Rutgers, Robert Wood Johnson Medical School Newark, New Jersey, United States
Background: In infants with perinatally depressed but preserved circulation, the use of O2 for resuscitation (Rs) is not recommended. In animal models of circulatory arrest (CA), Rs with O2 vs RA is not superior in achieving a return of spontaneous circulation (ROSC). However, compared to RA, Rs with O2 significantly raised cerebral oxygenation. Objective: In neonatal mice with hypoxic CA, the initiation of Rs with O2 versus RA restores cerebral oxidative-phosphorylation (OXPHOS) significantly faster. This is beneficial for neurological outcome. Design/Methods: P10 intubated, anesthetized mice with ligated right carotid artery were ventilated with 5% oxygen until Doppler flowmetry-defined CA. After 60 sec of CA, mice were Rs by mechanical ventilation with either RA (n=62) or O2 (n=61). The rate and time to ROSC were recorded. At 0, 5, 30 and 240 min of reperfusion (Rep) mitochondria (M) were isolated from the ipsilateral (ipsi) and contralateral (contra) hemispheres (h) and their NAD-linked respiration was measured. At 5 days of Rep, brains were Nissl stained and the extent of injury (RA, n=26; O2, n=26) was assessed. Results: No differences in the incidence and time to ROSC was detected. At the end of CA (before Rep), compared to naives, M ADP-phosphorylating respiration and respiratory control ratio (RCR) were dramatically (p < 0.0001) and equally depressed in both h. At 5 min of Rep, in O2-Rs mice, M from both h recovered significantly (p≤0.01) greater compared to RA-Rs mice. At 30 and 240 min of Rep, M function nearly fully recovered and did not differ between groups. Regardless of the mode of Rs, at 240 min of Rep, organelles from the ipsi-h performed significantly poorer compared to the contra-h. The injury was detected only in the ipsi-h with 70.2±6.3% (Mean±SEM) of residual tissue volume in RA-Rs and 82.6±4.5% in O2-Rs mice (p=0.12). The extent of damage by the injury score was significantly (p < 0.05) greater in the thalamus and striatum in RA-Rs mice with no difference in the cortex (p=0.2) and hippocampus (p=0.07), compared to O2-Rs mice.
Conclusion(s): Asphyxia with 60 sec of CA severely inhibits cerebral OXPHOS, but without ligation of the carotid artery does not cause brain injury. Considering similar rate/time to ROSC and severity of OXPHOS depression in both groups, but a significantly faster bioenergetic recovery and a trend toward lessened extent of brain injury in O2-Rs vs RA-Rs mice, we speculate that the pace of metabolic recovery contributes to the mechanisms defining cellular fate. We continue testing the hypothesis with a proper sample size.
