The role of histamine in the increased cardiac output in hyperdynamic endotoxemia.

The role of histamine in the hyperdynamic circulatory response to endotoxin (ETX) was investigated in 32 anesthetized dogs by means of histamine H1- and H2-receptor blockade. A hyperdynamic circulation was elicited with a prolonged, slow infusion of a low dose of ETX, and hemodynamic parameters were examined in control and histamine receptor-blocked groups. The following groups were studied: Group ETX received a 2 h infusion of Escherichia coli 055:B5 endotoxin in a total dose of 13.75 micrograms/kg at a rate of 10 micrograms/kg for 45 min and then 5 micrograms/kg for 75 min. In addition to the same dose of ETX, Groups ETX+TPA and ETX+RAN received 0.5 mg/kg of the H1-blocker tripelennamine (TPA) or 2 mg/kg of the H2-blocker ranitidine (RAN), respectively. Infusion of ETX caused a moderate decrease in arterial pressure in Group ETX, whereas TPA but not RAN inhibited this pressure fall. The cardiac output (CO) increased by 41% above the baseline level in Group ETX. Both TPA and RAN prevented this rise in CO. The total peripheral resistance was considerably lowered by ETX, but this decrease was significantly attenuated in the TPA or RAN-treated groups. The heart rate rose significantly after ETX infusion and was unaffected by TPA or RAN. The stroke volume remained unchanged following ETX but was decreased both by TPA and by RAN. TPA or RAN, when given alone, did not affect any of the measured hemodynamic parameters. These experiments provide evidence of the participation of histamine in the hyperdynamic circulatory response in endotoxemia.