Effect of histamine receptor antagonists on mortality in compound 48/80-induced shock

The roles of histamine and H1 and H2 receptors in shock are uncertain. We have found that treatment of aged rats with compound 48/80 (a mast cell degranulator) produced lethal (LD99) shock which was completely prevented by lodoxamide (LOD), a mast cell degranulation inhibitor. This study evaluated the effect of H1 and H2 receptors and age on mortality of 48/80-induced shock in rats. To assess survival, 65 young male (125 g), 65 mature male (250 g) and 30 aged male (500 g) SD rats were placed in groups and treated intraperitoneally with saline; 48/80; LOD + 48/80; the H1 blocker diphenhydramine (DPH) + 48/80; the H2 blocker cimetidine (CIM) + 48/80; or DPH and CIM + 48/80. Rats were observed for 30 min or until death. All 125 g rats survived. Of the 250 g rats, 50% of 48/80-treated and 100% of CIM + 48/80-treated rats died; all others survived. All 500 g 48/80- and CIM + 48/80-treated rats died; all other 500 g rats survived. For all ages, survival differences between saline-, 48/80-, and CIM + 48/80-treated rats were highly significant (P less than or equal to 0.0001). In addition, both 48/80 and CIM + 48/80 greatly reduced mean survival time in the 250 g and 500 g groups (P less than or equal to 0.0001) compared to all other treatments. Both LOD and DPH were protective against 48/80, and DPH was also protective against CIM + 48/80, for both absolute survival and mean survival time (P less than or equal to 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)