Mild Hypothermia Attenuates the Excitatory Amino Acids Overflow and Diminishes the Nitric Oxide Synthase Activity during Reperfusion after Asphyxial Cardiac Arrest in Rats.

Aims: Neurotransmitter overflow into the extracellular space and activation of nitric oxide synthase were implicated in neuronal death after cerebral ischemia. A small temperature reduction induced after the insult crucially mitigated the neuronal death. To elucidate the mechanisms, dopamine and glutamate as marker of excitatory amino acid (EAA) overflow and the citrulline/arginine ratio (CAR) as marker of nitric oxide synthase were analysed. Study Design: Animal experiments in rats. Place and Duration of the Study: Laboratory of the Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels between 2001 and 2003. Methodology: Striatal Glutamate and dopamine and CAR were measured by using microdialysis under normothermic and hypothermic conditions before asphyxial cardiac arrest, during the insult and resuscitation as well as during the weaning process from mechanical ventilation. Results: After the insult, the EAA overflow increased significantly in the normothermic group. In the hypothermic group, however this overflow was not significantly different from the sham group. The CAR increased up to 5-fold compared to the basal value in the normothermic group and only 2.5-fold in the hypothermic group. The brain damage was mitigated in the hypothermic group, while this increased further up 7 days after the insult in the normothermic group. Conclusion: These results suggest that the neuroprotective effect of mild hypothermia resides in attenuation of the striatal EAA overflow and diminution of the CAR and were associated with a reduction of brain damage at 24 hours and 7 days post insult.

Antiatherogenic effect of a low lysine: arginine ratio of protein involves alteration in the aortic glycosamihoglycans and glycoproteins.

The effect of alteration of lysine: arginine ratio of the protein on the aortic glycosaminoglycans and glycoproteins was studied in rats fed cholesterol free and atherogenic diet. The concentration of total glycosaminoglycans and of individual fractions was significantly lower in the aorta in the case of diet with lysine: arginine ratio of 1·0, than the diet with a ratio of 2·0. Rats fed globulin fraction isolated from sesame seeds, which has a lysine: arginine ratio of 0·67 also showed significantly lower concentration of total and individual glycosaminoglycan fractions in the aorta than those fed casein (lysine:arginine ratio 2·0). Concentration of total hexose and fucose in the glycoproteins was also lower in the aorta in the case of lysine: arginine ratio 1·0. These results in the light of previous reports of increase in the aortic glycosaminoglycans in the early stages of atherosclerosis and increase in the total hexose and fucose in the glycoproteins in the atherosclerotic aorta indicate that the antiatherogenic effect of a low lysine: arginine ratio in the protein involves alteration in the aortic glycosaminoglycans and glycoproteins.