Top

Published in:

01-05-2011 | Review Article

Assessment of coronary endothelial function using PET

Authors: Keiichiro Yoshinaga, MD, PhD, FACC, Osamu Manabe, MD, PhD, Nagara Tamaki, MD, PhD

Published in: Journal of Nuclear Cardiology | Issue 3/2011

Abstract

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. Several coronary risk factors adversely affect endothelial function. Therefore, a finding of endothelial dysfunction may guide interventions for preventing the development of future cardiovascular events. The non-invasive aspects and coronary specificity of measurements of myocardial blood flow (MBF) using positron emission tomography (PET) with sympathetic stress make it widely applicable for the evaluation of endothelial function. PET MBF measurements with sympathetic stress have been applied to a variety of subjects with coronary risk factors and have been shown to have value for risk assessment in these subjects. Endothelial measurement using PET remains an ideal research tool for the study of the pathophysiology of several cardiac diseases. PET is also well suited for the acute and longitudinal evaluation of treatment. Thus, the continued development of this approach for the evaluation of new treatment effects should be expected.

Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002;105:546-9.PubMedCrossRef

Lerman A, Zeiher AM. Endothelial function: Cardiac events. Circulation 2005;111:363-8.PubMedCrossRef

Ganz P, Vita JA. Testing endothelial vasomotor function: Nitric oxide, a multipotent molecule. Circulation 2003;108:2049-53.PubMedCrossRef

Beanlands RS, Youssef G. Diagnosis and prognosis of coronary artery disease: Pet is superior to spect: Pro. J Nucl Cardiol 2010;17:683-95.PubMedCrossRef

Yoshinaga K, Chow BJ, Dekemp RA, Thorn S, Ruddy TD, Davies RA, et al. Application of cardiac molecular imaging using positron emission tomography in evaluation of drug and therapeutics for cardiovascular disorders. Curr Pharm Des. 2005;11:903-32.PubMedCrossRef

Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356:830-40.PubMedCrossRef

Schelbert HR. Anatomy and physiology of coronary blood flow. J Nucl Cardiol 2010;17:545-54.PubMedCrossRef

Yoshinaga K, Tamaki N, Ruddy T, DeKemp RA, Beanlands R. Evaluation of myocardial perfusion. In: Wahl R, editors. Principles and practice of pet and pet/ct, 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2009. p. 541-64.

Yoshinaga K, Manabe O, Katoh C, Chen L, Klein R, Naya M, et al. Quantitative analysis of coronary endothelial function with generator-produced 82rb pet: Comparison with 15o-labelled water pet. Eur J Nucl Med Mol Imaging 2010;37:2233-41.PubMedCrossRef

10.

Moncada S. Nitric oxide: Discovery and impact on clinical medicine. J R Soc Med 1999;92:164-9.PubMed

11.

Kelly JJ, Whitworth JA. Endothelin-1 as a mediator in cardiovascular disease. Clin Exp Pharmacol Physiol 1999;26:158-61.PubMedCrossRef

12.

Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: Testing and clinical relevance. Circulation 2007;115:1285-95.PubMed

13.

Pijls NH, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 1996;334:1703-8.PubMedCrossRef

14.

Celermajer DS. Reliable endothelial function testing: At our fingertips? Circulation 2008;117:2428-30.PubMedCrossRef

15.

Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ, et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999;99:3234-40.PubMed

16.

Lanza GA, Crea F. Primary coronary microvascular dysfunction: Clinical presentation, pathophysiology, and management. Circulation 2010;121:2317-25.PubMedCrossRef

17.

Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation 2003;108:2054-9.PubMedCrossRef

18.

Tamaki N, Yoshinaga K, Naya M. Coronary vasomotor function assessed by positron emission tomography. Eur J Nucl Med Mol Imaging 2010;37:1213-24.PubMedCrossRef

19.

Bengel FM, Higuchi T, Javadi MS, Lautamaki R. Cardiac positron emission tomography. J Am Coll Cardiol 2009;54:1-15.PubMedCrossRef

20.

deKemp RA, Yoshinaga K, Beanlands RS. Will 3-dimensional pet-ct enable the routine quantification of myocardial blood flow? J Nucl Cardiol 2007;14:380-97.PubMedCrossRef

21.

Campisi R, Czernin J, Schoder H, Sayre JW, Marengo FD, Phelps ME, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation 1998;98:119-25.PubMed

22.

Iwado Y, Yoshinaga K, Furuyama H, Ito Y, Noriyasu K, Katoh C, et al. Decreased endothelium-dependent coronary vasomotion in healthy young smokers. Eur J Nucl Med Mol Imaging 2002;29:984-90.PubMedCrossRef

23.

Klein R, Beanlands RS, deKemp RA. Quantification of myocardial blood flow and flow reserve: Technical aspects. J Nucl Cardiol 2010;17:555-70.PubMedCrossRef

24.

Schindler TH, Schelbert HR, Quercioli A, Dilsizian V. Cardiac pet imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC Cardiovasc Imaging 2010;3:623-40.PubMedCrossRef

25.

Yoshinaga K, Manabe O, Tamaki N. Physiological assessment of myocardial perfusion using nuclear cardiology would enhance coronary artery disease patient care. Circulation J 2011;75:713-23.CrossRef

26.

Slart RH. Coronary endothelial function: A clinical role for pet? Eur J Nucl Med Mol Imaging 2010;37:2231-2.PubMedCrossRef

27.

Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, Schafers KP, Luscher TF, Camici PG. Coronary heart disease in smokers: Vitamin c restores coronary microcirculatory function. Circulation 2000;102:1233-8.PubMed

28.

Kawano H, Motoyama T, Ohgushi M, Kugiyama K, Ogawa H, Yasue H. Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina. Ann Intern Med 2001;135:977-81.PubMed

29.

Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002;105:804-9.PubMedCrossRef

30.

Machac J, Bacharach SL, Bateman TM, Bax JJ, Beanlands R, Bengel F, et al. Positron emission tomography myocardial perfusion and glucose metabolism imaging. J Nucl Cardiol 2006;13:e121-51.PubMedCrossRef

31.

Buus NH, Bottcher M, Hermansen F, Sander M, Nielsen TT, Mulvany MJ. Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia. Circulation 2001;104:2305-10.PubMedCrossRef

32.

DePuey EG, editor. Imaging guidelines for nuclear cardiology procedures, Part 2. American society of nuclear cardiology. J Nucl Cardiol 1999;6:G47-84.

33.

Furuyama H, Odagawa Y, Katoh C, Iwado Y, Yoshinaga K, Ito Y, et al. Assessment of coronary function in children with a history of kawasaki disease using (15)o-water positron emission tomography. Circulation 2002;105:2878-84.PubMedCrossRef

34.

Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: A new form of acute, reversible heart failure. Circulation 2008;118:2754-62.PubMedCrossRef

35.

Ghiadoni L, Donald AE, Cropley M, Mullen MJ, Oakley G, Taylor M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation 2000;102:2473-8.PubMed

36.

Martin EA, Prasad A, Rihal CS, Lerman LO, Lerman A. Endothelial function and vascular response to mental stress are impaired in patients with apical ballooning syndrome. J Am Coll Cardiol 2010;56:1840-6.PubMedCrossRef

37.

Martin EA, Tan SL, MacBride LR, Lavi S, Lerman LO, Lerman A. Sex differences in vascular and endothelial responses to acute mental stress. Clin Auton Res 2008;18:339-45.PubMedCrossRef

38.

Schoder H, Silverman DH, Campisi R, Sayre JW, Phelps ME, Schelbert HR, et al. Regulation of myocardial blood flow response to mental stress in healthy individuals. Am J Physiol Heart Circ Physiol 2000;278:H360-6.PubMed

39.

Schoder H, Silverman DH, Campisi R, Karpman H, Phelps ME, Schelbert HR, et al. Effect of mental stress on myocardial blood flow and vasomotion in patients with coronary artery disease. J Nucl Med 2000;41:11-6.PubMed

40.

Arrighi JA, Burg M, Cohen IS, Kao AH, Pfau S, Caulin-Glaser T, et al. Myocardial blood-flow response during mental stress in patients with coronary artery disease. Lancet 2000;356:310-1.PubMedCrossRef

41.

Lovallo W. The cold pressor test and autonomic function: A review and integration. Psychophysiology 1975;12:268-82.PubMedCrossRef

42.

Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: Importance of the functional integrity of the endothelium. J Am Coll Cardiol 1989;14:1181-90.PubMedCrossRef

43.

Peckerman A, Hurwitz BE, Saab PG, Llabre MM, McCabe PM, Schneiderman N. Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response. Psychophysiology 1994;31:282-90.PubMedCrossRef

44.

Schindler TH, Nitzsche EU, Olschewski M, Brink I, Mix M, Prior J, et al. Pet-measured responses of mbf to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography. J Nucl Med 2004;45:419-28.PubMed

45.

Di Carli MF, Tobes MC, Mangner T, Levine AB, Muzik O, Chakroborty P, et al. Effects of cardiac sympathetic innervation on coronary blood flow. N Engl J Med 1997;336:1208-15.PubMedCrossRef

46.

Prior JO, Schindler TH, Facta AD, Hernandez-Pampaloni M, Campisi R, Dahlbom M, et al. Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans. Eur J Nucl Med Mol Imaging 2007;34:20-7.PubMedCrossRef

47.

Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al. Repeatability of cold pressor test-induced flow increase assessed with h(2)(15)o and pet. J Nucl Med 2006;47:1420-6.PubMed

48.

Pop-Busui R, Kirkwood I, Schmid H, Marinescu V, Schroeder J, Larkin D, et al. Sympathetic dysfunction in type 1 diabetes: Association with impaired myocardial blood flow reserve and diastolic dysfunction. J Am Coll Cardiol 2004;44:2368-74.PubMedCrossRef

49.

Jansky L, Matouskova E, Vavra V, Vybiral S, Jansky P, Jandova D, et al. Thermal, cardiac and adrenergic responses to repeated local cooling. Physiol Res 2006;55:543-9.PubMed

50.

LeBlanc J, Dulac S, Cote J, Girard B. Autonomic nervous system and adaptation to cold in man. J Appl Physiol 1975;39:181-6.PubMed

51.

LeBlanc J, Cote J, Dulac S, Dulong-Turcot F. Effects of age, sex, and physical fitness on responses to local cooling. J Appl Physiol 1978;44:813-7.PubMed

52.

Hilz MJ, Axelrod FB, Braeske K, Stemper B. Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia. J Neurol Sci 2002;196:81-9.PubMedCrossRef

53.

Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, et al. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol 2005;45:1505-12.PubMedCrossRef

54.

Naya M, Tsukamoto T, Morita K, Katoh C, Furumoto T, Fujii S, et al. Olmesartan, but not amlodipine, improves endothelium-dependent coronary dilation in hypertensive patients. J Am Coll Cardiol 2007;50:1144-9.PubMedCrossRef

55.

Czernin J, Muller P, Chan S, Brunken RC, Porenta G, Krivokapich J, et al. Influence of age and hemodynamics on myocardial blood flow and flow reserve. Circulation 1993;88:62-9.PubMed

56.

Prior JO, Quinones MJ, Hernandez-Pampaloni M, Facta AD, Schindler TH, Sayre JW, et al. Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation 2005;111:2291-8.PubMedCrossRef

57.

Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 1994;24:471-6.PubMedCrossRef

58.

Bottcher M, Botker HE, Sonne H, Nielsen TT, Czernin J. Endothelium-dependent and -independent perfusion reserve and the effect of l-arginine on myocardial perfusion in patients with syndrome x. Circulation 1999;99:1795-801.PubMed

59.

Di Carli MF, Janisse J, Grunberger G, Ager J. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 2003;41:1387-93.PubMedCrossRef

60.

Schelbert HR. Coronary circulatory function abnormalities in insulin resistance: Insights from positron emission tomography. J Am Coll Cardiol 2009;53:S3-8.PubMedCrossRef

61.

Momose M, Abletshauser C, Neverve J, Nekolla SG, Schnell O, Standl E, et al. Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus. Eur J Nucl Med Mol Imaging 2002;29:1675-9.PubMedCrossRef

62.

Quinones MJ, Hernandez-Pampaloni M, Schelbert H, Bulnes-Enriquez I, Jimenez X, Hernandez G, et al. Coronary vasomotor abnormalities in insulin-resistant individuals. Ann Intern Med 2004;140:700-8.PubMed

63.

Bengel FM, Abletshauser C, Neverve J, Schnell O, Nekolla SG, Standl E, et al. Effects of nateglinide on myocardial microvascular reactivity in type 2 diabetes mellitus-a randomized study using positron emission tomography. Diabet Med 2005;22:158-63.PubMedCrossRef

64.

Schindler TH, Cadenas J, Facta AD, Li Y, Olschewski M, Sayre J, et al. Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus. Eur Heart J 2009;30:3064-73.PubMedCrossRef

65.

Morita K, Tsukamoto T, Naya M, Noriyasu K, Inubushi M, Shiga T, et al. Smoking cessation normalizes coronary endothelial vasomotor response assessed with 15o-water and pet in healthy young smokers. J Nucl Med 2006;47:1914-20.PubMed

66.

Naya M, Morita K, Yoshinaga K, Manabe O, Goto D, Hirata K, et al. Long-term smoking causes more advanced coronary endothelial dysfunction in middle-aged smokers compared to young smokers. Eur J Nucl Med Mol Imaging 2011;38:491-8.PubMedCrossRef

67.

Yoshinaga K, Chow BJ, Williams K, Chen L, deKemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol 2006;48:1029-39.PubMedCrossRef

68.

Schindler TH, Cardenas J, Prior JO, Facta AD, Kreissl MC, Zhang XL, et al. Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function. J Am Coll Cardiol 2006;47:1188-95.PubMedCrossRef

69.

Yoshinaga K, Klein R, Tamaki N. Generator-produced rubidium-82 positron emission tomography myocardial perfusion imaging-from basic aspects to clinical applications. J Cardiol 2010;55:163-73.PubMedCrossRef

70.

Campisi R, Nathan L, Pampaloni MH, Schoder H, Sayre JW, Chaudhuri G, et al. Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration. Circulation 2002;105:425-30.PubMedCrossRef

Title: Assessment of coronary endothelial function using PET
Authors: Keiichiro Yoshinaga, MD, PhD, FACC
Osamu Manabe, MD, PhD
Nagara Tamaki, MD, PhD
Publication date: 01-05-2011
Publisher: Springer-Verlag
Published in: Journal of Nuclear Cardiology / Issue 3/2011
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI: https://doi.org/10.1007/s12350-011-9370-3

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Assessment of coronary endothelial function using PET

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2011

Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance

Cme instructions: Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance

Stress echocardiography for the detection and assessment of coronary artery disease

The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality

Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells

Low-dose and long-term G-CSF treatment can improve severe myocardial ischemia in patients with severe coronary artery disease

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page