Cerebral mitochondrial and regional haemoglobin saturation patterns during and after profound hypothermic circulatory arrest in neonatal piglets

Introduction

Total circulatory arrest (TCA) in deep hypothermia used in corrective surgery of complex cardiovascular malformations in children has been claimed to cause brain injury and altered psychomotor development.Near infrared spectroscopy (NIRS) allows in vivo determination of changes in cerebral oxygenated (HbO₂), deoxygenated (Hb), and total haemoglobin (Hbt; the sum of Hb + HbO₂). Relative changes in the redox state of cytochrome oxydase (cyt.aa3), the terminal enzyme in the mitochondrial respiratory chain, may provide information about the availability of oxygen at cellular level. The new tissue oxygenation index (TOI) provides information on the global tissue oxygenation. Measurement of protein S-100 is used as a marker of astroglial cell injury. Thus, change in intravascular and intracellular oxygenation states were measured by NIRS during and after TCA in a neonatal piglet model.

Method

Fourteen neonatal piglets (age > 10 days, weight 1.9 ± 0.25 kg) were anaesthetised, intubated and mechanically ventilated. Cardiopulmonary bypass (CPB) was performed using a uniform perfusion method: full flow CPB (200 ml/kg per min), minimal temperature (14 ± 1.3 °C), pCO₂ uncorrected for hypothermia (α-stat method). TCA was induced after establishment of a hypothermic rectal temperature of 14-16 °C. After warm reperfusion, the animals were weaned and monitored for 8 h. Cerebral oxygenation monitor (Hamamatsu 300, Herching-Deutschland) was used to obtain online measurement of cerebral oxidation parameters. Simultaneous hemodynamic parameters were continuously documented.

Results

In all animals significant initial increase in HbO₂, Hbt and TOI, and fall in cyt.aa3 and Hb were found during cooling on bypass. After induction of TCA in deep hypothermia a significant initial continuous parallel decrease in HbO₂, Hbt, TOI and cyt.aa3, and increase in Hb, followed by a plateau trend without further significant change, were found. An initial restoration of the oxidation parameters was associated with reperfusion and rewarming. However, after the end of reperfusion the oxygenation parameters, particularly cyt.aa3 and TOI were significantly reduced for 60 min.

Conclusion

Distinct related changes in intravascular and intracellular cerebral oxygenation patterns were found during cooling and after TCA. The delayed recovery of cyt.aa3 signal after TCA may indicate increased oxygen demand after hypothermic TCA.