Breakdown of adenine nucleotides, formation of oxygen free radicals, and early markers of cellular injury in endotoxic shock.

OBJECTIVE

To study the influence of shock on muscle and plasma adenine nucleotide and creatine pools and their metabolites, and to identify early markers of cellular injury in shock.

SETTING

Surgical research laboratory, Kuwait and UAE.

DESIGN

Experimental study.

MATERIAL: 19 New Zealand rabbits.

INTERVENTIONS: 15 rabbits were injected with Escherichia coli endotoxin, and an additional 4 rabbits acted as controls.

MAIN OUTCOME MEASURES: Blood and muscle energy metabolites, platelet count, arterial blood gas tensions, and arterial pressure were followed until the animals died.

RESULTS

Five minutes after injection of endotoxin muscle ATP, creatine phosphate, and total adenine purine concentration decreased. This decrease was later reversed, but again decline to a critical level in the terminal phase. Loss of the muscle creatine pool indicated cellular damage after 3 hours. Plasma hypoxanthine, creatine, and lactate concentrations increased continuously throughout the study.

CONCLUSION

Hypoxanthine formation is a possible source of oxygen free radicals in shock. The rise of hypoxanthine, creatine, and lactate concentrations in plasma during septic shock may reflect early high energy nucleotide failure, membrane injury, and anaerobic metabolism, respectively.