Skip to main content

Advertisement

SpringerLink
Log in

Pharmacologic stress testing: New methods and new agents

  • Published:
Journal of Nuclear Cardiology Aims and scope

Conclusions

The combination of vasodilators with exercise stress testing can be used safely and effectively, with improved image quality and with significant reduction of problematic side effects. Dobutamine may be used in patients with bronchospastic lung disease and has an acceptable side effect profile.

Selective A2A receptor agonists are potent coronary vasodilators that should not produce significant hypotension. This selectivity will also likely reduce side effects and AV block produced by stimulation of the other adenosine receptor subtypes, making these agents highly desirable for pharmacologic stress testing. Importantly, if as expected these new A2A agonists do not produce bronchoconstriction, then they can be used safely in virtually all patients. The results from experimental studies appear promising for A2A receptor agonists, and clinical trials of these agents are now under way.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. AMR data, 2002.

  2. Coma-Canella I. Dobutamine stress test to diagnose the presence and severity of coronary artery lesions in angina. Eur Heart J 1991;12:1198–204.

    PubMed  CAS  Google Scholar 

  3. Mazeika PK, Nadazdin A, Oakley CM. Dobutamine stress echocardiography for detection and assessment of coronary artery disease. J Am Coll Cardiol 1992;19:1203–11.

    PubMed  CAS  Google Scholar 

  4. Previtali M, Lanzarini L, Ferrario M, et al. Dobutamine versus dipyridamole echocardiography in coronary artery disease. Circulation 1991;83(Suppl 3):27–31.

    Google Scholar 

  5. Martin TW, Seaworth JF, John JP, et al. Comparison of adenosine, dipyridamole and dobutamine in stress echocardiography. Ann Intern Med 1992;116:190–6.

    PubMed  CAS  Google Scholar 

  6. Elhendy A, Valkema R, van Domburg RT, et al. Safety of dobutamine-atropine stress myocardial perfusion scintigraphy. J Nucl Med 1998;39:1662–6.

    PubMed  CAS  Google Scholar 

  7. Geleijnse ML, Elhendy A, Fioretti PM, Roelandt JR. Dobutamine stress myocardial perfusion imaging. J Am Coll Cardiol 2000;36:2017–277.

    Article  PubMed  CAS  Google Scholar 

  8. Wu JC, Yun JJ, Heller EN, et al. Limitations of dobutamine for enhancing flow heterogeneity in the presence of single coronary stenosis: implications for technetium-99m-sestamibi imaging. J Nucl Med 1998;39:417–25.

    PubMed  CAS  Google Scholar 

  9. Calnon DA, Glover DK, Beller GA, et al. Effects of dobutamine stress on myocardial blood flow, 99mTc sestamibi uptake, and systolic wall thickening in the presence of coronary artery stenoses. Implications for dobutamine stress testing. Circulation 1997; 96:2353–60.

    PubMed  CAS  Google Scholar 

  10. Geleijnse ML, Elhendy A, van Domburg RT, et al. Prognostic significance of normal dobutamine-atropine stress sestamibi scintigraphy in women with chest pain. Am J Cardiol 1996;77:1057- 61.

    Article  PubMed  CAS  Google Scholar 

  11. Calnon DA, McGrath Paul D, Doss AL. Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: strati- fication of a high-risk population. J Am Coll Cardiol 2001;38:1511–77.

    Article  PubMed  CAS  Google Scholar 

  12. Kiat H, Iskandrian AS, Villegas BJ, Starling MR, Berman DS. Arbutamine stress thallium-201 single photon emission computed tomography using a computerized closed-loop delivery system. Multicenter trial for evaluation of safety and diagnostic accuracy. J Am Coll Cardiol 1995;26:1159–67.

    Article  PubMed  CAS  Google Scholar 

  13. Marchant E, Pichard AD, Casanegra P, Lindsay J. Effect of intravenous dipyridamole on regional coronary blood flow with 1-vessel coronary artery disease: evidence against coronary steal. Am J Cardiol 1984;53:718–21.

    Article  PubMed  CAS  Google Scholar 

  14. DePuey EG, Rozanski A. Pharmacological and other nonexercise alternatives to exercise testing to evaluate myocardial perfusion and left ventricular function with radionuclides. Semin Nucl Med 1991;21:92–101.

    Article  PubMed  CAS  Google Scholar 

  15. Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation 1990;82:1595–606.

    PubMed  CAS  Google Scholar 

  16. Fung AY, Gallagher KP, Buda AJ. The physiologic basis of dobutamine as compared with dipyridamole stress interventions in the assessment of critical coronary stenosis. Circulation 1987;76:943–511.

    PubMed  CAS  Google Scholar 

  17. Feldman R, Nichols W, Pepine C, et al. Acute effect of intravenous dipyridamole on regional coronary hemodynamics and metabolism. Circulation 1981;64:333–44.

    PubMed  CAS  Google Scholar 

  18. Lette J, Tatum JL, Fraser S, et al. Safety of dipyridamole testing in 73,806 patients: the Multicenter Dipyridamole Safety Study. J Nucl Cardiol 1995;2:3–17.

    Article  PubMed  CAS  Google Scholar 

  19. Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging; results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994;23:384–90.

    PubMed  CAS  Google Scholar 

  20. Nguyen T, Heo J, Ogilby JD, Iskandrian AS. Single photon emission computed tomography with thallium-201 during adenosine- induced coronary hyperemia: correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography. J Am Coll Cardiol 1990;16:1375–83.

    PubMed  CAS  Google Scholar 

  21. Borges-Neto S, Mahmarian JJ, Jain A, Roberts S, Verani MS. Quantitative thallium-201 single photon emission computed tomography after oral dipyridamole for assessing the presence, anatomic location and severity of coronary artery disease. J Am Coll Cardiol 1988;11:962–9.

    PubMed  CAS  Google Scholar 

  22. Beer SG, Heo J, Kong B, et al. Use of oral dipyridamole SPECT thallium-201 imaging in detection of coronary artery disease. Am Heart J 1989;118(Pt I):1022–7.

    Article  Google Scholar 

  23. Nishimura S, Mahmarian JJ, Boyce TM, Verani MS. Quantitative thallium-201 single photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease. J Am Coll Cardiol 1991;18:736–45.

    Article  PubMed  CAS  Google Scholar 

  24. Iskandrian AS, Heo J, Nguyen T, et al. Tomographic myocardial perfusion imaging with technetium-99m teboroxime during adenosine- induced coronary hyperemia: correlation with thallium-201 imaging. J Am Coll Cardiol 1992;19:307–12.

    PubMed  CAS  Google Scholar 

  25. Ruddy TD, Dighero HR, Newell JB, et al. Quantitative analysis of dipyridamole-thallium images for detection of coronary artery disease. J Am Coll Cardiol 1987;10:142–9.

    PubMed  CAS  Google Scholar 

  26. Ladenheim ML, Pollock BH, Rozanski A, et al. Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease. J Am Coll Cardiol 1986; 7:464–71.

    Article  PubMed  CAS  Google Scholar 

  27. Brown KA, Heller GV, Landin RS. Early dipyridamole (99m)Tcsestamibi single photon emission computed tomographic imaging 2 to 4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events: comparison with submaximal exercise imaging. Circulation 1999;100:2060–6.

    PubMed  CAS  Google Scholar 

  28. Treuth MG, Reyes GA, He ZX, et al. Tolerance and diagnostic accuracy of an abbreviated adenosine infusion for myocardial scintigraphy: a randomized prospective study. J Nucl Cardiol 2001;8:548–54.

    Article  PubMed  CAS  Google Scholar 

  29. O’Keefe JH Jr, Bateman TM, Handlin LR, Barnhart CS. Four- versus 6-minute infusion protocol for adenosine thallium-201 single photon emission computed tomography imaging. Am Heart J 1995;129:482–7.

    Article  PubMed  Google Scholar 

  30. Villegas BJ, Hendel RC, Dahlberg ST. Comparison of a 3- versus 6-minute infusion of adenosine in thallium-201 myocardial perfusion imaging. Am Heart J 1993;126:103–7.

    Article  PubMed  CAS  Google Scholar 

  31. Jamil G, Ahlberg AW, Elliott MD, et al. Impact of limited treadmill exercise on adenosine Tc-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging in coronary artery disease. Am J Cardiol 1999;84:400–3.

    Article  PubMed  CAS  Google Scholar 

  32. Reyes GA, He ZX, Verani MS. Adenosine myocardial SPECT for detection of coronary artery disease: a comparison of 3 and 6 minute protocol [abstract]. J Am Coll Cardiol 1998;31:518A-9A.

    Article  Google Scholar 

  33. Ignaszewski AP, McCormick LX, Heslip PG, McEwan AJ, Humen DP. Safety and clinical utility of combined intravenous dipyridamole/ symptom-limited exercise stress test with thallium-201 imaging in patients with known or suspected coronary artery disease. J Nucl Med 1993;34:2053–61.

    PubMed  CAS  Google Scholar 

  34. Cramer MJ, Verzijibergen JF, van der Wall EE, et al. Comparison of adenosine and high-dose dipyridamole both combined with low-level exercise stress for 99Tcm-MIBI SPET myocardial perfusion imaging. Nucl Med Commun 1996;17:97–104.

    Article  PubMed  CAS  Google Scholar 

  35. Casale PN, Guiney TE, Strauss HW, Boucher CA. Simultaneous low level treadmill exercise and intravenous dipyridamole stress thallium imaging. Am J Cardiol 1988;62(10 Pt 1):799–802.

    Article  PubMed  CAS  Google Scholar 

  36. Stern S, Greenberg ID, Corne R. Effect of exercise supplementation on dipyridamole thallium-201 image quality. J Nucl Med 1991;32:1559–64.

    PubMed  CAS  Google Scholar 

  37. Pennell DJ, Mavrogeni SI, Forbat SM, Karwatowski SP, Underwood SR. Adenosine combined with dynamic exercise for myocardial perfusion imaging. J Am Coll Cardiol 1995;25:1300–9.

    Article  PubMed  CAS  Google Scholar 

  38. Thomas GS, Prill NV, Majmundar H, et al. Treadmill exercise during adenosine infusion is safe, results in fewer adverse reactions, and improves myocardial perfusion image quality. J Nucl Cardiol 2000;7:439–6.

    Article  PubMed  CAS  Google Scholar 

  39. Elliott MD, Holly TA, Leonard SM, Hendel RC. Impact of an abbreviated adenosine protocol incorporating adjunctive exercise on adverse effects and image quality in patients undergoing stress myocardial perfusion imaging. J Nucl Cardiol 2000;7:584–9.

    Article  PubMed  CAS  Google Scholar 

  40. Gould KL. Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilatation: I. Physiologic basis and experimental validation. Am J Cardiol 1978;41:267–78.

    Article  PubMed  CAS  Google Scholar 

  41. Gould KL, Westcott RJ, Albro PC, Hamilton GW. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation: II. Clinical methodology and feasibility. Am J Cardiol 1978;41:279–87.

    Article  PubMed  CAS  Google Scholar 

  42. Albro PC, Gould KL, Westcott RJ, et al. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation: III. Clinical trial. Am J Cardiol 1978;42:751–60.

    Article  PubMed  CAS  Google Scholar 

  43. L’Abbate A. Pathophysiological basis for noninvasive functional evaluation of coronary stenosis. Circulation 1991;83(Suppl 3):III2–7.

    PubMed  CAS  Google Scholar 

  44. Marcus ML, Wilson RF, White CW. Methods of measurement of myocardial blood flow in patients: a critical review. Circulation 1987;76:245–53.

    PubMed  CAS  Google Scholar 

  45. Chambers CE, Brown KA. Dipyridamole-induced ST segment depression during thallium-201 imaging in patients with coronary artery disease: angiographic and hemodynamic determinants. J Am Coll Cardiol 1988;12:37–41.

    Article  PubMed  CAS  Google Scholar 

  46. Meerdink DJ, Okada RD, Leppo JA. The effect of dipyridamole on transmural blood flow gradients. Chest 1989;96:400–5.

    Article  PubMed  CAS  Google Scholar 

  47. Verani MS, Mahmarian JJ. Myocardial perfusion scintigraphy during maximal coronary artery vasodilation with adenosine. Am J Cardiol 1991;67:12D-7D.

    Article  PubMed  CAS  Google Scholar 

  48. Bertolet BD, Belardinelli L, Franco EA, et al. Selective attenuation by N-0861 (N6-endonorboran-2-yl-9-methyladenine) of cardiac A1 adenosine receptor-mediated effects in humans. Circulation 1996;93:1871–66.

    PubMed  CAS  Google Scholar 

  49. Nagashima S, Moore HJ, Kerensky R. Dose ranging study of N-0861, a selective A1 adenosine receptor antagonist, in patients receiving adenosine [abstract]. J Am Coll Cardiol 1994;23:874A.

    Google Scholar 

  50. Gaspardone A, Crea F, Versaci F. Muscular and cardiac adenosineinduced pain is mediated by A1 receptors. J Am Coll Cardiol 1995;25:251–70.

    Article  PubMed  CAS  Google Scholar 

  51. Martin PL, Ueeda M, Olsson RA. 2-Phenylethoxy-9-methyladenine: an adenosine receptor antagonist that discriminates between A2 adenosine receptors in the aorta and the coronary vessels from the guinea pig. J Pharmacol Exp Ther 1993;265:248–53.

    PubMed  CAS  Google Scholar 

  52. Linden J, Thai T, Figler H, Jin X, Robeva AS. Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol 1999;56:705–13.

    PubMed  CAS  Google Scholar 

  53. Auchampach JA, Jin X, Wan TC, Caughey GH, Linden J. Canine mast cell adenosine receptors: cloning and expression of the A3 receptor and evidence that degranulation is mediated by the A2B receptor. Mol Pharmacol 1997;52:846–60.

    PubMed  CAS  Google Scholar 

  54. Liu GS, Richards SC, Olsson RA, et al. Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart. Cardiovasc Res 1994;28:1057–61.

    Article  PubMed  CAS  Google Scholar 

  55. Reeves JJ, Jones CA, Sheehan MJ, Vardey CJ, Whelan CJ. Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo. Inflamm Res 1997;46:180–4.

    Article  PubMed  CAS  Google Scholar 

  56. Glover DK, Ruiz M, Sansoy V, Barrett RJ, Beller GA. Effect of N-0861, a selective adenosine A1 receptor antagonist, on pharmacologic stress imaging with adenosine. J Nucl Med 1995;36:270–5.

    PubMed  CAS  Google Scholar 

  57. Ueeda M, Thompson RD, Arroyo LH, Olsson RA. 2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor. J Med Chem 1991;34:1334–9.

    Article  PubMed  CAS  Google Scholar 

  58. Webb RL, Sills MA, Chovan JP. CGS-21680: a potent selective adenosine A2 receptor agonist. Cardiovasc Drug Rev 1992;1:26–53.

    Article  Google Scholar 

  59. Niiya K, Olsson RA, Thompson RD, Silvia SK, Ueeda M. 2-(N’-alkylidenehydrazino) adenosines: potent and selective coronary vasodilators. J Med Chem 1992;35:4557–61.

    Article  PubMed  CAS  Google Scholar 

  60. Rieger JM, Brown ML, Sullivan GW, Linden J, Macdonald TL. Design, synthesis, and evaluation of novel A2A adenosine receptor agonists. J Med Chem 2001;44:531–9.

    Article  PubMed  CAS  Google Scholar 

  61. Murphree LJ, Marshall MA, Rieger JM, Macdonald TL, Linden J. Human A(2A) adenosine receptors: high-affinity agonist binding to receptor G protein complexes containing G-beta(4). Mol Pharmacol 2002;61:455–62.

    Article  PubMed  CAS  Google Scholar 

  62. He ZX, Cwajg E, Hwang W, et al. Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A) receptor agonist. Circulation 2000;102:438–44.

    PubMed  CAS  Google Scholar 

  63. Glover DK, Ruiz M, Yang JY, et al. Pharmacological stress thallium scintigraphy with 2-cyclohexylmethylidenehydrazinoadenosine (WRC-0470). A novel, short-acting adenosine A2A receptor agonist. Circulation 1996;94:1726–32.

    PubMed  CAS  Google Scholar 

  64. Trochu JN, Gong Zhao, Xiaobin Xu. Selective A2A adenosine receptor agonist for pharmacological stress testing during myocardial perfusion imaging [abstract]. J Am Coll Cardiol 2001;37:412AA.

    Google Scholar 

  65. Sullivan GW, Reiger J, Scheld M, et al. Cyclic AMP-dependent inhibition of human neutrophil oxidative activity by substituted 2-propynylcyclohexyl adenosine A2A receptor agonists. Br J Pharmacol 2001;132:1017–26.

    Article  PubMed  CAS  Google Scholar 

  66. Glover DK, Ruiz M, Takehana K, et al. Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection. Circulation 2001;104:1181–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rush-Presbyterian-St. Luke’s Medical Center, 1725 W Harrison Ave, Suite 020, 60612, Ill., Chicago

    Robert C. Hendel

  2. Cook County Hospital, Chicago, Ill

    Tariq Jamil

  3. University of Virginia Health System, Charlottesville, Va

    David K. Glover

Authors
  1. Robert C. Hendel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tariq Jamil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David K. Glover
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert C. Hendel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hendel, R.C., Jamil, T. & Glover, D.K. Pharmacologic stress testing: New methods and new agents. J Nucl Cardiol 10, 197–204 (2003). https://doi.org/10.1067/mnc.2003.5

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1067/mnc.2003.5

Keywords

Search

Navigation