Effects of a combined drug regimen on tumour necrosis factor and plasma kallikrein activity in experimental endotoxaemia.

OBJECTIVE

To clarify the relationship between changes in haemodynamics, liberation of tumour necrosis factor and generation of plasma kallikrein, and to see if treatment with a combination of drugs was successful in preventing activation of tumour necrosis factor and plasma kallikrein in experimental endotoxic shock.

DESIGN

Controlled study.

MATERIAL: 22 juvenile pigs.

INTERVENTIONS: 15 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline. 10 received no treatment, and 5 were given a combination of methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin.

MAIN OUTCOME MEASURES: Assessment of the liberation of tumour necrosis factor, generation of plasma kallikrein, and haemodynamic and cellular effects of endotoxaemia.

RESULTS

There was a linear statistical relationship between decreases in cardiac output and increases in packed cell volume, and between increases in packed cell volume and plasma kallikrein activity. The combination treatment totally blocked all the effects of the infusion of endotoxin.

CONCLUSION

Endotoxin affects several mediators, but combination treatment can prevent some of these effects.