Date of Award

1977

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

John J. DeFeo

Abstract

Ventricular fibrillation is one of the primary causes of early sudden death associated with myocardial infarction (Lown et al. 1959). Although Bellet et al. 1972) have shown that caffeine infusion increases susceptibility to ventricular fibrillation in the dog, the question of the effect of daily caffeine consumption on cardiac vulnerability remains unanswered. Retrospective clinical studies examining the association of coffee consumption on heart disease cloud the long term effect of caffeine on cardiac vulnerability to arrhythmia in that they are often complicated by differences in each group's level of cigarette smoking, blood pressure, body weight, etc. In this study the effects of long term caffeine administration on the heart to ventricular fibrillation susceptibility of was examined. Vulnerability to cardiac arrhythmia in the adult male rat was determined by measuring the ventricular tachycardia threshold (VTT). The VTT was used as an index of the vulnerability of larger hearts to fibrillation. It was defined as the minimum current necessary to generate sustained ventricular tachycardia, and was tested by applying trains of pulses directly to the right ventricular epicardium through bipolar platinum electrodes. The train consisted of constant current, 70 Hz, monophaslc, 2 msec rectangular pulses. It was delivered 10 msecs after the right atrial pacing pulse and lasted 90 msecs so as to end before the apex of the T wave of the electrocardiogram. In rats receiving a single oral injection of caffeine (30 or 90 mg/kg) VTT was 25 per cent lower than the VTT of water injected rats (p <0.05). The oral injection of water reduced VTT by 35% when compared with untreated controls. The caffeine related reduction was in addition to that associated with the injection process. Corresponding tachycardia suggested that the injection process, in addition to the caffeine administration, was associated with sympathetic discharge which presumably mediated the reduction in threshold. Daily oral treatment with caffeine (in the same doses) for 2, 4, 8 or 10 weeks caused a time related reversal of the acute effects of caffeine injection. Following 2 or 4 weeks of treatment, acute caffeine administration no longer was associated with a reduction in VTT. After 8 or 10 weeks of chronic caffeine administration, acute caffeine injection was associated with thresholds more than twice as great as water treated controls. This relative increase In VTT following chronic caffeine was dose dependent. The increase in VTT following chronic caffeine administration was the same magnitude whether the rat was injected just prior to VTT testing with water or with caffeine. Caffeine injection (90 mg/kg/day, p.o.) for a period of 10 weeks attenuated the maximal chronoscopic effect of isoproterenol. This result suggested a reduction in cardiac beta adrenergic receptor concentration. The reduction in the vulnerability of the rat ventricle to tachyarrhythmia associated with chronic caffeine administration, may be due to the same reduction in the cardiac adrenergic receptor population.

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