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-preceptor blockade and calcium channel blockade. Two groups of rabbits were used, those fed a normal diet and those fed a high cholest...

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Bibliographic Details
Published in:Cardiovascular research 1985-12, Vol.19 (12), p.744-753
Main Authors: TOZZI, C A, DORRELL, S G, MERRILL, G F
Format: Article
Language:English
Subjects:
Animals
Arteriosclerosis - pathology
Arteriosclerosis - physiopathology
atherosclerosis
Biological and medical sciences
Ca2+ channel blockers
Cardiology. Vascular system
chlorpheniramine
Chlorpheniramine - pharmacology
Cimetidine - pharmacology
Coronary Circulation - drug effects
Coronary Disease - etiology
Coronary Disease - physiopathology
Coronary heart disease
coronary vasospasm
Coronary Vessels - drug effects
Coronary Vessels - pathology
Coronary Vessels - physiopathology
Heart
histamine
Histamine - pharmacology
Male
Medical sciences
myocardial ischaemia
Rabbits
Verapamil - pharmacology
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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
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/19.12.744