Histamine H|3 activation depresses cardiac function in experimental sepsis
In the heart, histamine H$\sb3$ receptors may function as inhibitory heteroreceptors that downregulate norepinephine exocytosis in pathological conditions associated with enhanced sympathetic neural activity. In sepsis, there is intense adrenergic stimulation as cardiovascular collapse develops over the course of the illness. Intense adrenergic stimulation may lead to histamine release and activation of cardiac H$\sb3$ receptors. Inhibition of cardiac adrenergic responses could lead to a relative decrease in cardiac output contributing to cardiovascular collapse in a gram-negative sepsis. In the present study, it was hypothesized that H$\sb3$ receptor blockade might improve cardiovascular function in sepsis. In a canine model of E. coli sepsis, it was observed that after 4 hrs of bacteremia, the H$\sb3$ receptor blocker (thioperamide maleate or clobenproprit) caused an increase in cardiac output (3.6 to 5.3 L/min; p $<$ 0.05) and blood pressure (mean 76 to 96 mmHg, p $<$ 0.05) compared with pretreatment values. In the cardiac mechanics study, H$\sb3$ receptor blockade improved left ventricular contractility in sepsis. Plasma histamine concentrations increased in the H$\sb3$ blocker/sepsis group as compared with a nonsepsis time control group. In a ventricular trabecular preparation, H$\sb3$ receptor blockade caused an increase in the adrenergic response in the presence of septic plasma. The present study shows that activation of H$\sb3$ receptors may contribute to cardiovascular collapse in sepsis.