Age related response of cerebral mitochondrial oxygenation in neonates and infants undergoing circulatory arrest in deep hypothermia

Introduction

Total circulatory arrest in deep hypothermia required in corrective cardiac surgery of complex congenital heart defects such as hypoplastic left heart syndrome (HLHS) in early life has been claimed to cause brain injury and altered psychomotor development. Determination of the changes in the regional intravascular concentration of oxygenated (HbO₂) and deoxygenated hemoglobin (Hb) by near infrared spectroscopy (NIRS) may provide noninvasive information about change in cerebral intravascular blood oxygenation. Relative change in the redox state of the cytochromeoxydase (cyt.aa3), the terminal enzyme in the mitochondrial respiratory chain that accounts for 90% of oxygen utilization in aerobic metabolism, may provide information about the availability of oxygen at cellular level.

The aim of this study therefore was to evaluate the patterns of changes in intravascular and intracellular oxygenation states in neonates with HLHS and infants with other congenital heart defects, undergoing corrective cardiac surgery using TCA in deep hypothermia.

Methods

Eight neonates with HLHS, median age 10 days (3-21), weight (3.3 ± 0.25 kg), and 9 infants with other diagnosis of congenital heart defects, median age 3.6 month (1-8), weight (4.7 ± 3.6-7 kg), were included in this study. Cardiac surgery was performed using uniform perfusion and anesthesia methods: full-flow CPB (120-150 ml/kg/min), minimal rectal temperature (16 ± 1.3°C), and minimal hemoglobin concentration (7± 1.5 mg/dl). Management of acid-base status during CPB was performed according to the alpha-stat method. Total circulatory arrest (TCA) was induced after establishment of a hypothermic blood temp at 12-15°C. Cerebral oxygenation monitor (Criticon cerebral redox monitor 2020, Johnson & Johnson) was used to obtain the on-line measurements of regional concentrations of cyt.aa3, HbO₂, tHb and Hb.

Results

There was a significant difference in the change of intravascular and intracellular oxygenation according to the post-natal age during full flow bypass and in the circulatory arrest time. A continuous parallel decrease of rSO₂ and HbO₂ were found in both groups during hypothermic TCA. However marked divergent change in the mitochondrial cyt.aa3 signal was noted between the neonates and the infants particularly during TCA. These discordant divergent patterns in the intracellular and intravascular NIRS signal continued also during reperfusion after TCA.

Conclusion

The main preliminary finding in this study was the paradoxical increased signal of mitochondrial cyt.aa3 during TCA in the neonates with HLHS in comparison to the infants despite the simultaneous relative decline in intravascular concentration of HbO₂ in both groups. The observed age dependent change in the cyt.aa3 patterns may indicate an alteration of oxygen metabolism at mitochondrial level and possible disturbance of electron transport of the oxidative pathway in deep hypothermic TCA.