HISTAMINE H-3 ACTIVATION DEPRESSES CARDIAC-FUNCTION IN EXPERIMENTAL SEPSIS

In the heart, histamine (H-3) receptors may function as inhibitory pre synaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized th at H-3-receptor blockade might improve cardiovascular function in seps is. In a canine model of Escherichia coli sepsis, we found that H-3-re ceptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left vent ricular contractility compared with pretreatment values. Plasma histam ine concentrations increased modestly in the H-3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H-3 activation could be identified un der conditions of septic plasma. We conclude that activation of H-3 re ceptors may contribute to cardiovascular collapse in sepsis.