The Effects of Caffeine on Blood Pressure and Heart Rate a Review

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Open Access

Peer-reviewed

Research Article

Caffeine Consumption and Heart Charge per unit and Claret Pressure Response to Regadenoson

• Abbas Bitar,
• Ronald Mastouri,
• Rolf P. Kreutz

x

• Published: June 22, 2015
• https://doi.org/10.1371/journal.pone.0130487

Figures

Abstract

Background

Current guidelines recommend that caffeinated products should be avoided for at least 12 hours prior to regadenoson assistants. We intended to examine the effect of caffeine consumption and of timing of last dose on hemodynamic effects after regadenoson assistants for cardiac stress testing.

Methods

332 subjects undergoing regadenoson stress testing were enrolled. Baseline characteristics, habits of coffee/caffeine exposure, baseline vital signs and change in heart rate, blood force per unit area, percent of maximal predicted eye rate, and percent modify in heart charge per unit were prospectively collected.

Results

Non-coffee drinkers (group 1) (73 subjects) and subjects who last drank java >24 hours (group iii) (139 subjects) prior to regadenoson did non demonstrate any difference in systolic blood pressure level, heart rate change, maximal predicted middle rate and percent modify in eye rate. Systolic blood pressure level change (fifteen.2±17.i vs. 7.two±10.2 mmHg, p = 0.001), heart rate change (32.2±14 vs. 27.3±ix.6 bpm, p = 0.038) and maximal predicted heart rate (65.five±xv.six vs. 60.vii±8.6%, p = 0.038) were significantly higher in non-java drinkers (group 1) compared to those who drank coffee 12–24 hours prior (group 2) (108 subjects). Subjects who drank coffee >24 hours prior (group 3) exhibited higher systolic blood pressure level alter (thirteen±xv.eight vs. seven±ten.2, p = 0.007), and middle rate change (32.1±fifteen.3 vs. 27.iii±9.6, p = 0.017) as compared to those who drank java 12–24 hours prior to testing (group 2).

Conclusions

Caffeine exposure 12–24 hours prior to regadenoson administration attenuates the vasoactive effects of regadenoson, as evidenced by a blunted rising in middle charge per unit and systolic blood force per unit area. These results suggest that caffeine exposure within 24 hours may reduce the effects of regadenoson administered for vasodilatory cardiac stress testing.

Citation: Bitar A, Mastouri R, Kreutz RP (2015) Caffeine Consumption and Heart Rate and Blood Pressure Response to Regadenoson. PLoS One 10(6): e0130487. https://doi.org/ten.1371/journal.pone.0130487

Editor: Claudio Borghi, University of Bologna, ITALY

Received: February 12, 2015; Accustomed: May 19, 2015; Published: June 22, 2015

Copyright: © 2015 Bitar et al. This is an open up access article distributed nether the terms of the Creative Commons Attribution License, which permits unrestricted utilize, distribution, and reproduction in whatsoever medium, provided the original author and source are credited

Data Availability: Patient level data are available through the Indiana University Schoolhouse of Medicine Institutional Review Board for researchers who meet the criteria for admission to confidential information.

Funding: This publication was made possible in part, with back up from the Indiana Clinical and Translational Sciences Institute funded, in part by Grant Number (U54-RR025761. Anantha Shekhar, PI) from the National Institutes of Wellness, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana CTSI Specimen Storage Facility which was funded in part past a NCRR construction grant (C06-RR020128-01. R.S. Fife, PI, K. Cornetta, Co-I). The project was supported by the Indiana University Health Values Grant, the Indiana University Health – Indiana University School of Medicine Strategic Enquiry Initiative, and the Methodist Inquiry Institute Showalter Grant for Cardiovascular Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors declare that they accept no competing interests.

Introduction

Myocardial perfusion imaging (MPI) has been extensively used for detecting coronary artery disease, assessing viable myocardium, and evaluating the effect of different therapeutic interventions [1]. Vasodilator stress testing accounts for up to 45% of MPI studies [2]. Adenosine and dipyridamole take been the principal vasodilators used for stress testing until 2008 when regadenoson was approved past the FDA [three]. Regadenoson is a selective adenosine A2A receptor agonist. It has a very low affinity for A1 adenosine receptors and almost no affinity for A2B and A3 adenosine receptors. Regadenoson'southward selectivity for A2A receptors results in increased vasodilation and later on increased coronary blood flow (CBF). It is administered at a fixed dose of 0.4mg as an intravenous bolus. It has a rapid onset of action and a curt duration of action with maximal plasma concentration achieved inside i to four minutes after administration and an initial half-life of two to 4 minutes. [4–6].

The American Society of Nuclear cardiology recommends confronting the consumption of caffeinated food andbeverages or foods containing other methylxanthines (chocolate) for at to the lowest degree 12 hours prior to regadenoson assistants (ASNC 2009). Caffeine, a (ane,three,7-trimethylxanthine), is a non-selective competitive inhibitor of all adenosine receptors particularly A2A receptors [7,eight].

Few studies assessed the interaction of regadenoson and caffeine. In conscious dogs, intravenous administration of caffeine at 1–10 mg/kg, followed past regadenoson injection 45 minutes subsequently, did not significantly affect regadenoson induced coronary blood flow (CBF), but reduced the duration of the 2-fold increase in CBF. It also blunted eye rate and claret pressure level change [nine]. In a randomized, placebo-controlled, double blind and crossover airplane pilot study of healthy subjects, Gaemperli et al. showed that moderate caffeine intake 2 hours prior to regadenoson administration did not bear upon myocardial blood flow (MBF) and blood pressure response but resulted in a blunted heart rate response [x]. In dissimilarity another randomized placebo controlled study demonstrated that administration of 200 or 400 mg of caffeine 90 minutes before regadenoson significantly reduced the number of segments with reversible defects by MPI [xi].

The effect and duration of caffeine exposure on blood pressure, heart rate, and percent of maximal predicted heart charge per unit among subjects undergoing pharmacological stress testing with regadenoson is not clear. We hypothesized that chronic caffeine intake with but 12–24 hours cessation prior to regadenoson stress testing according to drug labeling recommendation, affects maximal heart rate and claret pressure response as compared to non-caffeine consumption or more prolonged pause. The aim of the current written report is to assess the effect of habitual caffeine consumption on blood pressure, center charge per unit, percentage of predicted heart charge per unit and percentage change in heart rate among subjects undergoing vasodilator stress testing with regadenoson.

Methods

Patients

The written report protocol was canonical by the Indiana University institutional review board for inquiry. Written informed consent was obtained from all subjects. Subjects referred for regadenoson stress testing were enrolled. Patients with combined practise and regadenoson stress testing were excluded from analysis. Equally per the protocol of our institution, all patients were asked to not consume caffeinated beverages or xanthine containing foods for at least 12 hours prior to study. Moreover, all patients were asked to take their routine daily medications. Baseline demographic data and medical comorbidities were collected on all subjects. Information on amount, frequency, and final exposure to caffeine, chocolate, and caffeinated soft drinks were collected prospectively prior to performance of cardiac stress test. Caffeine exposure was classified according to none recently, last exposure of at least one cup of coffee 12–24 hours prior to regadenoson stress test, and >24 hours prior to stress test. Consumption of one cup of black or green tea was considered equal to one cup of java, and subjects who consumed tea were included in the java consumption group for assay. Subjects' heart charge per unit (HR), and blood pressure were recorded at baseline instantaneously before administration of regadenoson. Subjects remained in a supine position throughout the test. Change in center rate (changeHR) during the stress test was calculated by subtracting resting (restingHR) from peak heart rate (peakHR) recorded within five minutes after administration of regadenoson. Modify in systolic blood pressure level (changeSBP) was calculated by subtracting resting (restingSBP) from peak systolic blood force per unit area (peakSBP) recorded inside 5 minutes later administration of regadenoson. Maximal predicted center (MHR) charge per unit was calculated using 220-historic period (years) and per centum maximal predicted heart charge per unit (%MPHR) was calculated past peakHR over MHR and multiplying past 100 (%MPHR = (peakHR/MHR)*100). Percent alter in middle rate (%ChangeHR) was calculated by changeHR over restingHR and multiplying past 100. Incidence of patient reported side effects were prospectively recorded (dyspnea, nausea, flushing, dizziness, abdominal hurting, headache, breast pain).

Non-java drinkers (group i) were compared to subjects who had consumed java within 12 to 24 hours (group 2) or more 24 hours (group 3) prior to regadenoson assistants.

Statistical Analysis

Baseline demographic and clinical variables are descriptively summarized. Continuous variables are expressed as hateful ± SD. Chiselled data are presented as per centum frequency. Unpaired two-sided Student's t-test was used to compare normally distributed continuous data betwixt ii groups. I-way assay of variance test (ANOVA) and post hoc Tukey comparisons were used to decide difference between different groups based on coffee consumption. Chiselled variables were compared using the χ² test and continuous variables were computed using student t test. Statistical significance was divers as p-value < 0.05.

Multivariable linear regression with change in systolic blood pressure (SBP), 60 minutes, and pct maximal predicted middle rate achieved at tiptop exercise every bit outcome variables was performed for non-coffee drinkers, subjects exposed to coffee 12 to 24 hours and more than 24 hours earlier regadenoson administration. Exposure to java 12 to 24 hours prior was used equally the reference category. Adjustment for known confounders was based on clinical variables known to touch caffeine metabolism, as well as clinical variables with p<0.1 in univariable analysis and if adjustment for the variables resulted in at least a 10% modify in the estimate of the overall association.

Results

Baseline characteristics of the study subjects are described in (Table 1). Subjects mean age was 60±11 years. Among the subjects, 257 (78%) were coffee drinkers while 73 subjects denied any coffee consumption. Not-java drinkers tended to exist younger (57.ii±ten.5 vs. 60.nine±10.5 years, p = 0.01), more than obese (105.7±30.7 vs.97.3±23.5 Kg., p = 0.014), consumed less chocolate (69.9% vs. 80.9%, p = 0.042), had more GERD (41.ane% vs. 28.4%, p = 0.039) and were less frequently prescribed antiplatelet medication (37% vs. 52.9%, p = 0.016) as compared to coffee consumers. Twelve coffee drinkers did non report when they last consumed java. None of the subjects was taking theophylline. Table 1 summarizes baseline characteristics betwixt non-coffee drinkers (grouping 1), subjects who drank coffee 12–24 hours prior (group 2) and those who drank coffee more 24 hours to stress testing (grouping iii).

SBP modify (xv.ii±17.1 vs. seven.2±ten.2 mmHg, p = 0.001), HR change (32.2±14 vs. 27.3±9.half dozen bpm, p = 0.038) and %MPHR (65.5±15.6 vs. 60.7±8.vi%, p = 0.038) were significantly higher in non-coffee drinkers (group one) compared to those who drank java 12–24 hours prior (group 2). %Change HR (44.8±xix.7 vs. 40.7±15.76%, p = 0.377) was not significantly different between group 1 and two.

There was no significant deviation in SBP change (15.ii±17.1 vs. 13.01±xv.8 mmHg, p = NS), 60 minutes alter (32.two±14 vs. 32.one±15.three bpm, p = NS), %MPHR (65.5±xv.6 vs. 64.3±13.6%, p = NS), and %Change HR (44.viii±xix.7 vs. 46.8±23.7%, p = NS) betwixt non-coffee drinkers (group ane) and those who drank java >24 hours prior (group 3). Moreover, subjects who drank coffee >24 hours prior (group three) exhibited higher SBP change (13±15.8 vs. 7±10.two, p = 0.007) and HR change (32.ane±fifteen.iii vs. 27.3±9.half dozen, p = 0.017) equally compared to those who drank coffee 12–24 hours prior to testing (group 2). MPHR (64.3±13.6 vs. lx.7±8.vi%, p = 0.077) and %Change Hr (46.82±23.vii vs. 40.7±15.76%, p = 0.053) were college among grouping 3 compared to grouping 2 but failed to achieve statistical significance (Table 2) (Fig 1).

Fig one. Regadenoson Issue on SBP change, Hour change, %MPHR and % changeHR According to Coffee Consumption.

Grouping 1: non-coffee drinkers; Group 2: subjects who drank coffee 12–24 hours prior to stress examination; Group 3: subjects who drank coffee more than 24 hours prior to stress exam. Error confined correspond to 95% conviction interval.

https://doi.org/10.1371/journal.pone.0130487.g001

Later adjusting for age, race, weight, chocolate consumption, diuretics apply, history of coronary artery affliction, by myocardial infarction, asthma, calcium channel blocker and beta blocker utilize, Change SBP (p = 0.003), Change in HR (p = 0.046) and %MPHR (p = 0.015) remained significantly dissimilar betwixt non-coffee drinkers (grouping 1) and subjects who consumed coffee 12–24 hours prior (group 2) in multivariable regression assay. Moreover, on multivariable regression analysis, Change SBP (p = 0.031), Change HR (p = 0.019), and %Change 60 minutes (p = 0.041) remained significantly different betwixt subjects who drank java 12–24 hours (group 2) and subjects who drank coffee more than 24 hours prior.

Among subjects who drank coffee 12–24 hours (grouping 2) prior to regadenoson administration, the number of java drinks did non have any upshot on Change HR, Alter SBP, MPHR and %Change HR (Table 3).

The number of cocky-reported adverse furnishings was lower in subjects exposed to caffeine 12–24 hours prior to regadenoson (group 2), as compared to >24 hours prior (group three, or caffeine naïve subjects (group i)(1.35±1.i vs. 1.94±one.4 vs. ane.79±1.iv; p = 0.002). Group 2 adult less abdominal hurting (0.9% vs 16.iv% vs. 14.4%, p<0.001), nausea (12% vs. 28.8% vs. 26.6%, p = 0.007) and dizziness (17.6% vs. 32.9% vs. 38.1%, p = 0.002) when compared to groups 1 and 3.

Word

In our written report, subjects who were coffee naive (group 1) or those who consumed java more 24 hours prior (group 3) demonstrated significantly larger alter in heart charge per unit and systolic blood pressure when compared to subjects exposed to coffee within 12–24 hours (grouping two) prior to regadenoson exposure.

The blunted ascension in centre rate and systolic blood force per unit area observed in subjects with contempo exposure to caffeine may be attributed to the long caffeine one-half-life in some patients. Caffeine (1,three,7-trimethylxanthine) bioavailability is 100%, with peak level achieved within fifteen to 45 minutes [12]. Information technology is metabolized predominantly by cytochrome P450 (CYP1A2 isoenzyme) with a half live (t1/2) ranging between 2 to 12 hours [12,xiii]. Many atmospheric condition and medications accept been reported to affect caffeine metabolism and potentially impact its half-life. CYP450 inhibitors such as cimetidine, oral contraceptive usage, pregnancy, and alcoholic liver disease tin increase caffeine half-life [14–16]. CYP450 inducers, such every bit phenytoin, phenobarbital, or rifampin, also as smoking have been associated with a shortened caffeine half-life [17–xviii]. Caffeine is metabolized into iii agile metabolites: paraxanthine (one,seven-dimethylxanthine), theobromine (iii,7-dimethylxanthine) and theophylline (1,3-dimethylxatnhine)[19]. In humans, these metabolites account for 84%, 12% and 12% of caffeine metabolism respectively [20]. The half-life of paraxanthine, theobromine and theophylline can exist as high as 4, 7 and six hours respectively, and these active metabolites can therefore extend the biologic effects of caffeine exposure [21].

Caffeine is a competitive inhibitor of adenosine A1, A2A and A2B receptors [22]. Chronic inhibition of adenosine receptors by caffeine results in increased sensitivity and upward-regulation of those receptors [23,24]. Selective A2A receptors agonists, like regadenoson, are believed to increase middle rate past a reflex increase in sympathetic activity triggered past their vasodilatory effect on peripheral A2A receptors [25]. Notwithstanding, more than contempo evidence indicates a chemoreceptor mediated activation of the sympathetic nervous system and release of catecholamines [26,27]. In the coronary apportionment, at that place is a high reserve for A2A receptor mediated coronary vasodilation with 25% receptor occupancy by regadenoson translating into 90% maximal vasodilation [ten,28]. Thus minimal competitive inhibition by caffeine has been thought not to significantly impact maximal myocardial blood menses. In dissimilarity, in the peripheral vasculature, A2A receptor reserve may exist lower, thus possibly explaining a blunted increase in heart rate in response to regadenoson in subjects exposed to caffeine [10]

In addition, A2A receptors are nowadays in the atrium and are able to activate ryanodine receptors [29]. Ryanodine receptor activation and subsequent calcium release mediates beta adrenergic heart charge per unit stimulation [30]. 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 [31]. 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 charge per unit and blood pressure response could accept been in response to a combination of contradistinct sympathetic tone, variable chemoreceptor response, and vasodilatory effects by caffeine and regadenoson. We observed a decreased incidence of patient reported side effects in subjects exposed to caffeine between 12–24 hours supporting the possibility that residual caffeine activity attenuates the biologic response to regadenoson within this time window. It has been previously demonstrated that caffeine administered in doses of 200 or 400mg 90 minutes before regadenoson significantly reduces the sensitivity of MPI [11]. Following caffeine administration the mean number of reversible defects identified was reduced past approximately 60% [xi]. It is therefore possible that based on variations in caffeine metabolism, exposure to caffeine betwixt 12–24 hours earlier regadenoson could also reduce the sensitivity of regadenoson MPI. It may be necessary to hold caffeine consumption for 24 hours prior to regadenoson MPI to avert any residual interaction.

Our study had many limitations. Starting time, nosotros did not mensurate blood caffeine level and thus nosotros did not appraise the association between serum caffeine level and effect on 60 minutes, BP and %MPHR response. Second, patient recall bias of caffeine consumption might have contributed to our results. We could not command for the potential possibility of patients underreporting their caffeine consumption in order to avoid stress test delay or cancelation. Altered sympathetic tone, variable chemoreceptor response, as well equally vasodilatory effects past caffeine and regadenoson could have contributed to changes in heart charge per unit and blood force per unit area response. Moreover, it is difficult to appraise variations in caffeine dosing based on beverage types.

Conclusions

Caffeine exposure within 12–24 hours prior to regadenoson MPI seems to benumb the hemodynamic effect of regadenoson as indicated past blunting of heart rate and systolic blood pressure rise. Further studies are needed to examine the possible touch of caffeine exposure within 12–24 hours as currently endorsed in the FDA label on diagnostic sensitivity and specificity of regadenoson stress imaging.

Acknowledgments

This publication was made possible in part, with back up from the Indiana Clinical and Translational Sciences Found funded, in part past Grant Number (U54-RR025761. Anantha Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana CTSI Specimen Storage Facility which was funded in office by a NCRR construction grant (C06-RR020128-01. R.S. Fife, PI, K. Cornetta, Co-I). The project was supported past the Indiana University Health Values Grant, the Indiana University Wellness–Indiana Academy School of Medicine Strategic Enquiry Initiative, and the Methodist Research Institute Showalter Grant for Cardiovascular Research.

Author Contributions

Conceived and designed the experiments: AB RK RM. Performed the experiments: RK RM AB. Analyzed the data: RK RM AB. Contributed reagents/materials/analysis tools: RK RM AB. Wrote the newspaper: RK RM AB.

References

1. 1. Gaemperli O, Kaufmann PA. Lower dose and shorter acquisition: pushing the boundaries of myocardial perfusion SPECT. J Nucl Cardiol. 2011;18(5):830–2. pmid:21681614
   • View Article
   • PubMed/NCBI
   • Google Scholar
2. 2. Miyamoto MI, Vernotico SL, Majmundar H, Thomas GS. Pharmacologic stress myocardial perfusion imaging: a practical arroyo. J Nucl Cardiol. 2007;14(2):250–five. pmid:17386388
   • View Article
   • PubMed/NCBI
   • Google Scholar
3. three. Thompson CA. FDA approves pharmacologic stress agent. Am J Health Syst Pharm. 2008;65(x):890. pmid:18463333
   • View Article
   • PubMed/NCBI
   • Google Scholar
4. four. Cerqueira MD. Advances in pharmacologic agents in imaging: new A2A receptor agonists. Curr Cardiol Rep. 2006;8(ii):119–22. pmid:16524538
   • View Article
   • PubMed/NCBI
   • Google Scholar
5. v. Hsiao East, Ali B, Blankstein R, Skali H, Ali T, Bruyere J Jr., et al. Detection of Obstructive Coronary Artery Disease Using Regadenoson Stress and 82Rb PET/CT Myocardial Perfusion Imaging. J Nucl Med. 2013.
   • View Article
   • Google Scholar
6. 6. Buhr C, Gossl M, Erbel R, Eggebrecht H. Regadenoson in the detection of coronary avenue disease. Vasc Health Adventure Manag. 2008;four(2):337–twoscore. pmid:18561509
   • View Article
   • PubMed/NCBI
   • Google Scholar
7. vii. Belardinelli Fifty, Shryock JC, Snowdy Due south, Zhang Y, Monopoli A, Lozza G, et al. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther. 1998;284(3):1066–73. pmid:9495868
   • View Article
   • PubMed/NCBI
   • Google Scholar
8. 8. Kubo S, Tadamura E, Toyoda H, Mamede M, Yamamuro M, Magata Y, et al. Effect of caffeine intake on myocardial hyperemic catamenia induced by adenosine triphosphate and dipyridamole. J Nucl Med. 2004;45(5):730–eight. pmid:15136619
   • View Article
   • PubMed/NCBI
   • Google Scholar
9. 9. Zhao G, Messina Due east, Xu 10, Ochoa Thou, Lord's day HL, Leung Thousand, et al. Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist. J Cardiovasc Pharmacol. 2007;49(six):369–75. pmid:17577101
   • View Article
   • PubMed/NCBI
   • Google Scholar
10. 10. Gaemperli O, Schepis T, Koepfli P, Siegrist PT, Fleischman South, Nguyen P, et al. Interaction of caffeine with regadenoson-induced hyperemic myocardial claret catamenia as measured by positron emission tomography: a randomized, double-blind, placebo-controlled crossover trial. J Am Coll Cardiol. 2008;51(3):328–9. pmid:18206744
    • View Article
    • PubMed/NCBI
    • Google Scholar
11. xi. Tejani FH1 TR, Kristy R, Bukofzer Southward. Issue of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: a prospective, randomized, multicenter study. Int J Cardiovasc Imaging. 2014.
12. 12. Blanchard J, Sawers SJ. The absolute bioavailability of caffeine in human. Eur J Clin Pharmacol. 1983;24(i):93–8. pmid:6832208
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
13. 13. Balogh A, Harder South, Vollandt R, Staib AH. Intra-individual variability of caffeine elimination in healthy subjects. Int J Clin Pharmacol Ther Toxicol. 1992;30(10):383–seven. pmid:1304170
    • View Article
    • PubMed/NCBI
    • Google Scholar
14. 14. Patwardhan RV, Desmond PV, Johnson RF, Schenker Southward. Dumb elimination of caffeine by oral contraceptive steroids. J Lab Clin Med. 1980;95(iv):603–8. pmid:7359014
    • View Article
    • PubMed/NCBI
    • Google Scholar
15. 15. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther. 1982;31(5):656–61. pmid:7075114
    • View Article
    • PubMed/NCBI
    • Google Scholar
16. sixteen. Statland Be, Demas TJ. Serum caffeine half-lives. Healthy subjects vs. patients having alcoholic hepatic illness. Am J Clin Pathol. 1980;73(3):390–three. pmid:7361718
    • View Article
    • PubMed/NCBI
    • Google Scholar
17. 17. Parsons WD, Neims AH. Upshot of smoking on caffeine clearance. Clin Pharmacol Ther. 1978;24(1):xl–5. pmid:657717
    • View Article
    • PubMed/NCBI
    • Google Scholar
18. 18. Wietholtz H, Zysset T, Marschall HU, Generet K, Matern Southward. The influence of rifampin handling on caffeine clearance in healthy homo. J Hepatol. 1995;22(1):78–81. pmid:7751591
    • View Article
    • PubMed/NCBI
    • Google Scholar
19. 19. Jodynis-Liebert J, Flieger J, Matuszewska A, Juszczyk J. Serum metabolite/caffeine ratios as a test for liver role. J Clin Pharmacol. 2004;44(4):338–47. pmid:15051740
    • View Article
    • PubMed/NCBI
    • Google Scholar
20. 20. McLean C, Graham TE. Effects of exercise and thermal stress on caffeine pharmacokinetics in men and eumenorrheic women. J Appl Physiol. 2002;93(four):1471–8. pmid:12235049
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
21. 21. Lelo A, Birkett DJ, Robson RA, Miners JO. Comparative pharmacokinetics of caffeine and its main demethylated metabolites paraxanthine, theobromine and theophylline in homo. Br J Clin Pharmacol. 1986;22(2):177–82. pmid:3756065
    • View Article
    • PubMed/NCBI
    • Google Scholar
22. 22. Ralevic 5, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50(3):413–92. pmid:9755289
    • View Article
    • PubMed/NCBI
    • Google Scholar
23. 23. Conlay LA, Conant JA, deBros F, Wurtman R. Caffeine alters plasma adenosine levels. Nature. 1997;389(6647):136. pmid:9296490
    • View Article
    • PubMed/NCBI
    • Google Scholar
24. 24. Light-green RM, Stiles GL. Chronic caffeine ingestion sensitizes the A1 adenosine receptor-adenylate cyclase organisation in rat cerebral cortex. J Clin Invest. 1986;77(1):222–7. pmid:3003150
    • View Article
    • PubMed/NCBI
    • Google Scholar
25. 25. Alberti C, Monopoli A, Casati C, Forlani A, Sala C, Nador B, et al. Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists. J Cardiovasc Pharmacol. 1997;30(3):320–4. pmid:9300315
    • View Article
    • PubMed/NCBI
    • Google Scholar
26. 26. Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia acquired by A2A adenosine receptor agonists is mediated by straight sympathoexcitation in awake rats. J Pharmacol Exp Ther. 2006;316(2):695–702. pmid:16227469
    • View Article
    • PubMed/NCBI
    • Google Scholar
27. 27. Lieu Hard disk, Shryock JC, von Mering Go, Gordi T, Blackburn B, Olmsted AW, et al. Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol. 2007;xiv(4):514–20. pmid:17679059
    • View Article
    • PubMed/NCBI
    • Google Scholar
28. 28. Shryock JC, Snowdy S, Baraldi PG, Cacciari B, Spalluto G, Monopoli A, et al. A2A-adenosine receptor reserve for coronary vasodilation. Circulation. 1998;98(7):711–eight. pmid:9715864
    • View Article
    • PubMed/NCBI
    • Google Scholar
29. 29. Hove-Madsen L, Prat-Vidal C, Llach A, Ciruela F, Casado V, Lluis C, et al. Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release. Cardiovasc Res. 2006;72(2):292–302. pmid:17014834
    • View Article
    • PubMed/NCBI
    • Google Scholar
30. 30. Lakatta EG, Vinogradova TM, Bogdanov KY. Beta-adrenergic stimulation modulation of center rate via synchronization of ryanodine receptor Ca2+ release. J Card Surg. 2002;17(5):451–61. pmid:12630548
    • View Article
    • PubMed/NCBI
    • Google Scholar
31. 31. Tikh EI, Fenton RA, Dobson JG Jr. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts. Am J Physiol Heart Circ Physiol. 2006;290(1):H348–56. pmid:16143649
    • View Article
    • PubMed/NCBI
    • Google Scholar

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