Therapeutic hypothermia preserves the brain by reducing nitric oxide synthase after asphyxial cardiac arrest in rats

Introduction

Induced therapeutic hypothermia (TH) following cardiac arrest (CA) is the only strategy that has demonstrated improvement in outcomes. The mechanism by which TH, when applied after reperfusion, exerts its cell protective effect during CA remains unclear. The study aim was to elucidate the mechanisms; dopamine, glutamate as marker of excitatory amino acid overflow and also the citrulline/arginine ratio (CAR) as marker of nitric oxide synthase were measured during reperfusion after asphyxial CA in a sham operated group of rats, in a normothermic group and in a hypothermic group. Also the effect of TH on the histological data obtained from the rat's brain 24 hours and 7 days post insult were analyzed.

Methods

Anesthetized rats were exposed to 8 minutes of asphyxiation including 5 minutes of CA. The CA was reversed to restoration of spontaneous circulation, by brief external heart massage and ventilation within a period of 2 minutes.

Results

After the insult and during reperfusion, the extracellular concentration of glutamate and dopamine, as determined by microdialysis in the rat striatum, increased up to 3,000% and 5,000%, respectively, compared with the baseline values in the normothermic group. However, when TH was induced for a period of 60 minutes after the insult and restoration of spontaneous circulation, the glutamate and dopamine concentrations were not significantly different from that in the sham group. The CAR increased up to fivefold compared with the basal value in the normothermic group and only 2.5-fold in the hypothermic group. However, in the sham operated group this ratio remained low and stable throughout the experiment. Histological analysis of the brain showed that TH reduced brain damage, ischemic neurons, as well as astroglial cell proliferation.

Conclusion

TH induced after asphyxial CA mitigates the excitotoxic process, and diminishes nitric oxide synthase activity and brain damage as well as astroglial cell proliferation.