Evidence of histamine-induced myocardial ischaemia: Reversal by chlorpheniramine and potentiation by atherosclerosis

Summary: The effects of histamine on coronary vasomotor tone and on myocardial blood flow distribution were studied in the anaesthetised rabbit in the absence of histamine H₁-preceptor blockade and calcium channel blockade. Two groups of rabbits were used, those fed a normal diet and those fed a high cholesterol diet (2%) for 8 to 12 weeks. Continuous recordings of standard limb lead electrocardiograms (ECG) were obtained, and all animals were pretreated with cimetidine, an H₂-receptor blocker, to minimise the intervening systemic effects of histamine. In the absence of H₁-receptor blockade, histamine produced a marked (40 to 50%) reduction in coronary blood flow without significantly affecting other cardiovascular variables. This effect was seen uniformly across the free wall of the left ventricle, ie endo-epi flow ratios did not significantly change. Concomitant with the coronary vasoconstriction were significant depressions (≥0.1 mV) of the ECG ST-segment and elevation of cardiac tissue lactate and lactate:pyruvate ratio. These histamine-mediated responses were independently abolished by chlorpheniramine (1.5 mg·kg^-1 iv) and verapamil (0.5 mg·kg^-1 iv). Atherosclerosis reduced the average dose of histamine needed to induce these ischaemic changes from 55 ± 6 to 34 ± 6 μg·kg^-1·min^-1 (p<0.05). These findings suggest that in the H₂-receptor blocked rabbit coronary vascular bed histamine causes tissue ischaemia by an H₁-receptor mechanism. The decrement in myocardial blood flow appears to involve activation of plasma membrane calcium.