Evidence of histamine-induced myocardial ischaemia: reversal by chlorpheniramine and potentiation by atherosclerosis.
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-receptor 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 (greater than or equal to 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 X kg-1 iv) and verapamil (0.5 mg X kg-1 iv). Atherosclerosis reduced the average dose of histamine needed to induce these ischaemic changes from 55 +/- 6 to 34 +/- 6 micrograms X kg-1 X min-1 (p less than 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 channels and is sensitive to atherosclerosis.
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002744:Chlorpheniramine / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D014700:Verapamil