EFFECT OF COMBINED B-1 AND B-2 KININ RECEPTOR BLOCKADE IN PORCINE ENDOTOXIN-SHOCK

In order to investigate the contribution of kinin receptor antagonism in the treatment of LPS-induced shock we conducted a randomized study with anaesthetized piglets. Before randomization the animals were stra tified according to predetermined health criteria under baseline condi tions. One group of control animals received LPS from S. abortus equi (2 mu g/kg/h.i.v. for 8 h) and saline (Group 1). Another group receive d LPS and the B-2 antagonist CP-0127 (3 mu g/kg/min), beginning 1 h af ter LPS (Group 2). Group 3 received LPS and the B-2 antagonist in the aforementioned doses, and the B-1 antagonist io Leu(9)-des-Arg(10)-kal lidin (3 mu g/kg/min), also beginning 1 h after LPS. Overall survival figures after 8 h of LPS infusion were: Group 1, 10/22 (45%); Group 2, 10/17 (59%); Group 3, 10/28 (36%). Fifty percent (29/58) of animals t hat were healthy at baseline survived, but only 11% (1/9) of sick anim als survived (Log Rank p = 0.0001). In the subset of healthy animals, survival rates for Groups 2 and 3 were 77% and 38%, respectively (p = 0.0519). It appears, therefore, that B-2 blockade attenuates LPS-induc ed mortality whereas additional B-1 blockade seems to reverse these be neficial effects. This suggests that in this animal model the B-1 rece ptor does not serve the same purpose as the B-2 receptor, and that up- regulation of B-1 receptors during LPS shock may be an important mecha nism of host defence.