Skip to main content

Main menu

  • Home
  • Content
    • Current
      • JNMT Supplement
    • Ahead of print
    • Past Issues
    • Continuing Education
    • JNMT Podcast
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Rates
    • Journal Claims
    • Institutional and Non-member
  • Authors
    • Submit to JNMT
    • Information for Authors
    • Assignment of Copyright
    • AQARA Requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
    • Corporate & Special Sales
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNMT
    • JNM
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine Technology
  • SNMMI
    • JNMT
    • JNM
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Journal of Nuclear Medicine Technology

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • Continuing Education
    • JNMT Podcast
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Rates
    • Journal Claims
    • Institutional and Non-member
  • Authors
    • Submit to JNMT
    • Information for Authors
    • Assignment of Copyright
    • AQARA Requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
    • Corporate & Special Sales
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • Watch or Listen to JNMT Podcast
  • Visit SNMMI on Facebook
  • Join SNMMI on LinkedIn
  • Follow SNMMI on Twitter
  • Subscribe to JNMT RSS feeds
OtherCONTINUING EDUCATION

Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents

Elias H. Botvinick
Journal of Nuclear Medicine Technology March 2009, 37 (1) 14-25; DOI: https://doi.org/10.2967/jnmt.108.057802
Elias H. Botvinick
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • FIGURE 1. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 1. 

    Shown are pathways of adenosine production transport, receptor activation, and metabolism. (Adapted with permission of (10).)

  • FIGURE 2. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 2. 

    Four adenosine receptor subtypes—A1, A2A, A2B, and A3—have been characterized and cloned. Stimulation of these receptors accounts for varied effects on electrical conduction, vasodilation, and bronchoconstriction. Illustrated are several adenosine receptor agonists and physiologic responses that result from stimulation of selective receptor subtypes. Shown also are inhibitors of 2 pathways. (Adapted with permission of (28).)

  • FIGURE 3. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 3. 

    Shown are chemical compositions for regadenoson and binodenoson, compared with adenosine. Also presented are parameters of affinity and potency along with demonstration of its functional selectivity for A2A receptors. Affinity relates to tightness of binding of agent to receptor and its resultant duration of action. Adenosine is a low-affinity agent that is quickly released. Higher affinity of new and more specific A2A agonists does not seemingly interfere with preferential aminophylline binding and its use as antidote.

  • FIGURE 4. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 4. 

    Shown diagrammatically are clinical infusion protocols recommended for regadenoson and binodenoson. These are designed on the basis of pharmacokinetics of the agents and their necessary interaction with the imaging agent.

  • FIGURE 5. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 5. 

    (A) Shown is time course of changes in coronary blood flow with regadenoson (solid curve) and adenosine (dashed curve). (Adapted with permission of (33).) (B) Shown above line for dogs are incremental changes in coronary flow (QCX) noted with serial increases in binodenoson dosage, compared with adenosine dosage. Decremental changes in mean arterial pressure (MAP) are plotted below line. (Adapted with permission of (34).) (C) Shown is time course of changes in coronary conductance, coronary blood flow normalized for perfusion pressure, with regadenoson (red curve), binodenoson (green curve), adenosine (blue curve), and CGS-21680, an unsuccessful dilator that has been withdrawn. (Adapted with permission of (31).) (D) Shown is increased coronary flow with adenosine (left) and binodenoson, WRC-470 (right) in a dog with tight stenosis of left anterior descending (LAD) coronary artery but without evident left circumflex (LCX) disease. Flow at baseline is shown in black, and flow with respective dilators is shown with hatched bar. Note blunted LAD response; LCX responds fully, given presence of flow-limiting agent. The binodenoson seems to bring same or higher flow response. (Adapted with permission of (34).)

  • FIGURE 6. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 6. 

    (A) Correlations with 4 dosing regimens. Summed defect scores (SDS) generated with adenosine correlated well with those using binodenoson in a 1.5 μg/kg bolus dosage. (B) Shown are rest and stress adenosine and binodenoson perfusion images in 2 case examples (patients A and B). Agreement is apparent. (Adapted with permission of (30).)

  • FIGURE 7. 
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 7. 

    (A) Shown are agreement rates between adenosine–adenosine images (orange bars) and regadenoson–adenosine images (blue bars) based on presence or absence of reversible defects. Equality between these comparisons is evident. (B) Shown are agreement rates between adenosine–adenosine images (orange bars) and regadenoson–adenosine images (blue bars) by SSS, the summed stress score, based on a 17-segment model. Again, equality is evident. (C) Shown are SPECT images obtained with adenosine (top), with regadenoson (middle), and at rest (bottom) in 3 orthogonal views. Lateral reversible defect is seen on both sets of images and is more prominent with regadenoson. Rev. Def. = reversible defect. (Adapted with permission of (35).)

Tables

  • Figures
    • View popup
    TABLE 1

    Characteristics of Stress Ischemic Endpoints

    PerfusionWall motion
    Initial event in the ischemic cascadeFollows induced perfusion abnormality
    Does not require ischemiaRequires ischemia
    Specific indicator of ischemia or ischemic potentialNonspecific indicator of ischemia
    Not significantly affected by loading conditionsAffected by loading conditions
    Not significantly affected by resting wall motion abnormalitiesAffected by resting wall motion abnormalities
    Not generally affected by conduction abnormalitiesAffected by conduction abnormalities
    • Adapted from (3).

    • View popup
    TABLE 2

    Methods to Test CFR

    Direct tests of CFR (vasodilator stress agents)Indirect tests of CFR (exercise/dobutamine)
    Seek to provoke flow heterogeneitySeek to provoke ischemia (perfusion or wall motion abnormality)
    Best suited for perfusion endpointFits either perfusion or function ischemic endpoint (must be used with wall motion endpoint)
    Less likely influenced by antianginal drugsVary in ability to augment flow demands and test CFR
    Strongest, most reproducible, tests of CFRPermit serial function analysis
    • Adapted from (3).

    • View popup
    TABLE 3

    Physical, Chemical, and Clinical Characteristics of Current Pharmacologic Stress Agents

    Agent
    CharacteristicDipyridamoleAdenosineDobutamine
    SourceSyntheticNaturalSynthetic
    FDA approved for stress testingYesYesNo
    MechanismTests CFRTests CFRTrue ischemic stress
    Action on CFRIndirectDirectIndirect
    PreparationSimpleSimpleComplicated (requires trained nurse)
    Dosagemg/kgmg/kgmg/kg
    InfusionTimed pump (may be hand titrated)Timed/isolated intravenous sourcePump titration (requires trained nurse)
    Agent duration (half-life)Prolonged (∼90 min)Very short (12 s)Short (2.4 min)
    Intravenous line fails during infusionProblematicRedoProblematic
    Variable infusion rateTolerableIntolerableIntolerable
    Stress-test duration∼10–12 min∼4–8 min∼20–30 min
    Supervision and quality controlModestHighHigh
    Patient toleranceHighHighModerate
    Complications/side effectsBronchospasm/heart blockBronchospasm/heart blockIschemia/arrhythmia hypotension
    Symptom durationUsually briefBriefMay be prolonged
    SafetyLike exercise testLike exercise testLess than exercise test (only apply to selected patients)
    Safety with baseline dipyridamolePreservedReducedPreserved
    AntidoteAminophyllineDiscontinueβ-blocker
    Speed of reversalMinutesSecondsMinutes
    Diagnostic indicatorPerfusionPerfusionPerfusion/wall motion
    Prognostic valueHighHighModest
    Sensitivity with caffeineReducedReducedUnchanged
    Sensitivity with β-blockerReduced?Reduced?Reduced
    Prognosis with β-blockerEnhanced?Enhanced?Reduced
    • Adapted from (3).

    • View popup
    TABLE 4

    Chemical and Clinical Characteristics of New Selective A2A Agonists

    Selective A2A Agonists
    CharacteristicsCGS21680 (X)MRE-0470 BinodenosonATL-146e (X)CVT-3146 Regadenoson
    SelectivityLowHighVery highModerate
    AffinityHighHighHighModerate
    PotencyModerateHighVery highModerate
    StableYesYesYesYes
    Onset1–2 min1–2 min1–2 min<1 min
    Duration>20 min6–12 min10–20 min3 min
    Trials—2 (phase III)1 in 20032
    FDA approved—To be submitted—YES
    • Adapted with permission of (28).

    • View popup
    TABLE 5

    Adenosine and Regadenoson Symptoms

    SymptomAdenosine (n = 267)Regadenoson (n = 517)P (Fisher exact test)
    Any event210 (79)409 (79)0.93
    Any severe event18 (7)25 (5)0.32
    Flushing63 (24)86 (17)0.02
    Dyspnea49 (18)128 (25)0.05
    Headache42 (16)148 (29)<0.001
    Chest discomfort42 (16)57 (11)0.07
    Chest pain34 (13)41 (8)0.04
    Angina pectoris22 (8)40 (8)0.78
    Feeling hot17 (6)19 (4)0.10
    Nausea12 (4)29 (6)0.61
    Dizziness9 (3)35 (7)0.05
    Abdominal discomfort5 (2)32 (6)<0.01
    • Data are presented as number of patients, with percentage in parentheses. Medical Dictionary for Regulatory Activities–preferred terms reported by 5% of patients or more in either treatment at any time after start of infusion are shown. Symptoms did not vanish with regadenoson and, in fact, differed little in their frequency, compared with those related to adenosine administration. This similarity may be related, in part, to the methods applied to determine the presence of symptoms. Adapted with permission of (35).

    • View popup
    TABLE 6

    Adenosine and Regadenoson Tolerability

    QuestionTolerance levelAdenosineRegadenosonP (Cochran-Mantel-Haenszel test)
    How did you feel?<0.001
     Comfortable185 (32)200 (39)
     Slightly uncomfortable2133 (50)271 (52)
     Very uncomfortable338 (14)39 (8)
     Extremely uncomfortable411 (4)7 (1)
     Mean ± SE1.9 ± 0.051.7 ± 0.03
    How did this test compare with the first (open-label adenosine) test?<0.001
     Much better141 (15)177 (34)
     Somewhat better274 (28)129 (24)
     About the same3108 (40)126 (24)
     Somewhat worse430 (11)74 (14)
     Much worse514 (5)11 (2)
     Mean ± SE2.6 ± 0.062.3 ± 0.05
    • Data are presented as number of patients, with percentage in parentheses, unless otherwise indicated. When symptoms were considered for their tolerability, regadenoson showed a clear advantage. Adapted with permission of (35).

PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine Technology: 37 (1)
Journal of Nuclear Medicine Technology
Vol. 37, Issue 1
March 2009
  • Table of Contents
  • About the Cover
  • Index by author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine Technology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents
(Your Name) has sent you a message from Journal of Nuclear Medicine Technology
(Your Name) thought you would like to see the Journal of Nuclear Medicine Technology web site.
Citation Tools
Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents
Elias H. Botvinick
Journal of Nuclear Medicine Technology Mar 2009, 37 (1) 14-25; DOI: 10.2967/jnmt.108.057802

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents
Elias H. Botvinick
Journal of Nuclear Medicine Technology Mar 2009, 37 (1) 14-25; DOI: 10.2967/jnmt.108.057802
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Abstract
    • EXERCISE AND PHARMACOLOGIC STRESS TESTING FOR CAD EVALUATION
    • WHEN TO PERFORM PHARMACOLOGIC STRESS TESTING
    • THE MECHANISM OF CORONARY VASODILATOR STRESS TESTING
    • NONSELECTIVE A2A ADENOSINE RECEPTOR AGONISTS
    • DOBUTAMINE STRESS
    • SELECTIVE A2A ADENOSINE RECEPTOR AGONISTS
    • A SPECULATION
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Cardiac and coronary CT comprehensive imaging approach in the assessment of coronary heart disease
  • Google Scholar

More in this TOC Section

  • Illuminating the Hidden: Standardizing Cardiac MIBG Imaging for Sympathetic Dysfunction
  • PET/CT Case Series: Unmasking the Mystery of Cardiac Sarcoidosis
  • Delivery Methods of Radiopharmaceuticals: Exploring Global Strategies to Minimize Occupational Radiation Exposure
Show more Continuing Education

Similar Articles

SNMMI

© 2025 SNMMI

Powered by HighWire