predicted heart rate. % ChangeHR: percent change in heart rate Comparison among group 2 based on number of coffee drink consumed Caffeine and Regadenoson Response systolic blood pressure when compared to subjects exposed to coffee within 1224 hours prior to regadenoson exposure. The blunted rise in heart rate and systolic blood pressure observed in subjects with recent exposure to caffeine may be attributed to the long caffeine half-life in some patients. Caffeine bioavailability is 100%, with peak level achieved within 15 to 45 minutes. It is metabolized predominantly by cytochrome P450 with a half live ranging between 2 to 12 
hours. Many conditions and medications have been reported to affect caffeine metabolism and potentially affect PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19710468 its half-life. CYP450 inhibitors such as cimetidine, oral contraceptive usage, pregnancy, and alcoholic liver disease can increase caffeine half-life. CYP450 inducers, such as phenytoin, phenobarbital, or rifampin, as well as smoking have been associated with a shortened caffeine half-life. Caffeine is metabolized into 3 active metabolites: paraxanthine, theobromine and theophylline. In humans, these metabolites account for 84%, 12% and 12% of caffeine metabolism respectively. The half-life of paraxanthine, theobromine and theophylline can be as high as 4, 7 and 6 hours respectively, and these active metabolites can therefore extend the biologic effects of caffeine exposure. Caffeine is a competitive inhibitor of adenosine A1, A2A and A2B receptors. Chronic inhibition of adenosine receptors by caffeine results in increased sensitivity and up-regulation of those receptors. Selective A2A receptors agonists, like regadenoson, are believed to increase heart rate by a reflex increase in sympathetic activity Piclidenoson chemical information triggered by their vasodilatory effect on peripheral A2A receptors. However, more recent evidence indicates a chemoreceptor mediated activation of the sympathetic nervous system and release of catecholamines. In the coronary circulation, there is a high reserve for A2A receptor mediated coronary vasodilation with 25% receptor occupancy by regadenoson translating into 90% maximal vasodilation. Thus minimal competitive inhibition by caffeine has been thought not to significantly impact maximal myocardial blood flow. In contrast, in the peripheral vasculature, A2A receptor reserve may be lower, thus possibly explaining a blunted increase in heart rate in response to regadenoson in subjects exposed to caffeine In addition, A2A receptors are present in the atrium and are able to activate ryanodine receptors. Ryanodine receptor PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19711918 activation and subsequent calcium release mediates beta adrenergic heart rate stimulation. A2A receptor agonists have been shown to modulate the response to beta adrenergic stimulation by attenuating the effect of A1 receptor and increasing contractility directly. Therefore it is possible that caffeine exposure and partial inhibition of A2A receptors leads to decreased ryanodine receptor activation and blunting of beta adrenergic response mediated by A1 receptor. Our study findings suggest that consumption of caffeine within 24 hours may inhibit the vasodilatory properties of regadenoson administered for MPI. Moreover altered heart rate and blood pressure response could have been in response to a combination of altered sympathetic tone, variable chemoreceptor response, and vasodilatory effects by caffeine and regadenoson. We observed a decreased incidence of patient reported side effects