Contribution of Kinins to Endotoxin Shock in Unanesthetized Rhesus Monkeys

The effects of endotoxin (Escherichia coli and Pseudomonas pseudomallei) were studied in 18 unanesthetized rhesus monkeys restrained in primate chairs. Indwelling arterial and venous catheters were used for hemodynamic measurements and blood sampling. Whole blood kinin, plasma kininogen, lysosomal enzymes, complete blood counts, and blood gas tensions were measured. Within an hour of beginning the infusion of the endotoxin, the mean arterial pressure and systemic peripheral resistance decreased significantly in the 18 experimental monkeys compared to 13 control monkeys. These early changes were associated with significant elevation in whole blood kinin concentration and a decrease in plasma kininogen. All of these early changes were most marked in the animals that died. Granulocytopenia occurred within 15 minutes, and the concentration of free lysosomal enzyme in the plasma rose 2 hours after endotoxin infusion. The preterminal phase of shock was characterized by a low peripheral vascular resistance and decreasing cardiac output without elevation of kinin levels. These findings support the hypothesis that kinins play a pathogenetic role in the early phase of endotoxin-induced shock and that the severity of the early phase may influence the animalʼs survival. The relation of kinins to other vasoactive substances released after endotoxin-induced shock is unknown.