title: Evidence of histamine-induced myocardial ischaemia: reversal by chlorpheniramine and potentiation by atherosclerosis.
abstract: 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.
mesh_terms: 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
chemical_list: D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D014700:Verapamil