Effects of histamine H1-receptor stimulation on coronary hemodynamics in man

Abstract

Exogenous histamine in man induces significant cardiovascular effects mediated by activation of H1 and H2-receptors present on human heart and on coronary arteries. We studied the effects of selective H1-receptor stimulation on human coronary hemodynamics in 10 patients undergoing cardiac catheterization. All patients were pretreated with cimetidine before the histamine infusion (0.5 micrograms/kg/min i.v. for 5 min). Six of these patients had normal coronary arteries and four had single vessel coronary artery disease (CAD) and vasospastic angina. During the study heart rate was held constant (100 beats/min) by coronary sinus pacing. We measured mean aortic pressure (MAP), coronary sinus blood flow (CSBF), coronary vascular resistance (CVR) and myocardial oxygen consumption (MVO2) at rest, during histamine infusion, and 10 min after the end of the infusion. During infusion, MAP decreased from 103 +/- 5 to 85 +/- 6 mmHg (p less than 0.02) and CVR from 1.00 +/- 0.16 to 0.81 +/- 0.14 mmHg/ml/min (p less than 0.05); CSBF and MVO2 did not significantly change. All parameters returned to baseline at the end of the infusion. The response was similar in patients with normal coronary arteries and in 3 patients with CAD. Only one patient with CAD developed angina with ST segment elevation in D3, reduction in CSBF and an increase in CVR. These results indicate that H1-receptor stimulation in man induces significant coronary dilatation and that histamine infusion after cimetidine pretreatment is unlikely to provoke coronary spasm in patients with vasospastic angina.

Differential H1- and H2-receptor-mediated histamine responses of canine epicardial conductance and distal resistance coronary vessels.

“…'-2 -2 *" 31 When coronary blood flow is the measured variable, in situ and in vivo data indicate that histamine-induced increases are mediated by both H, and H 2 receptor. 4 -3 -32 - 33 While this apparent disparity in findings has produced some confusion, it does suggest a basis for the separate regulation and responsiveness of epicardial conductance and distal resistance arteries. Differential responsiveness of proximal and distal vessels to various vasoactive agents has been established.…”

Histamine and Human Heart

“…Thus, the net predominant effect of H 1 stim ulation on human coronary hemodynamics seems to be a reduction of CVR. However, in a small per centage of patients with coronary artery disease, the activation of H 1 receptors may result in an increase in CVR [15].…”