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Croteau E, Renaud JM, Archer C, et al. β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism. EJNMMI Res. 2014;4(1):68doi: 10.1186/s13550-014-0068-9.
Croteau, E., Renaud, J. M., Archer, C., Klein, R., DaSilva, J. N., Ruddy, T. D., Beanlands, R. S., & deKemp, R. A. (2014). β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism. EJNMMI research, 4(1), 68. https://doi.org/10.1186/s13550-014-0068-9
Croteau, Etienne, et al. "β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism." EJNMMI research vol. 4,1 (2014): 68. doi: https://doi.org/10.1186/s13550-014-0068-9
Croteau E, Renaud JM, Archer C, Klein R, DaSilva JN, Ruddy TD, Beanlands RS, deKemp RA. β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism. EJNMMI Res. 2014 Dec 16;4(1):68. doi: 10.1186/s13550-014-0068-9. eCollection 2014 Dec. PMID: 25621195; PMCID: PMC4293492.
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EJNMMI Res. 2014 Dec 16;4(1):68. doi: 10.1186/s13550-014-0068-9. eCollection 2014 Dec.

β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism.

EJNMMI research

Etienne Croteau, Jennifer M Renaud, Christine Archer, Ran Klein, Jean N DaSilva, Terrence D Ruddy, Rob Sb Beanlands, Robert A deKemp

Affiliations

  1. National Cardiac PET Centre, Department of Medicine, Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, K1Y 4W7 ON Canada.

PMID: 25621195 PMCID: PMC4293492 DOI: 10.1186/s13550-014-0068-9

Abstract

BACKGROUND: Endothelial dysfunction is associated with vascular risk factors such as dyslipidemia, hypertension, and diabetes, leading to coronary atherosclerosis. Sympathetic stress using cold-pressor testing (CPT) has been used to measure coronary endothelial function in humans with positron emission tomography (PET) myocardial blood flow (MBF) imaging, but is not practical in small animal models. This study characterized coronary vasomotor function in mice with [(11)C]acetate micro-PET measurements of nitric-oxide-mediated endothelial flow reserve (EFRNOM) (adrenergic-stress/rest MBF) and myocardial oxygen consumption (MVO2) using salbutamol β2-adrenergic-activation.

METHODS: [(11)C]acetate PET MBF was performed at rest + salbutamol (SB 0.2, 1.0 μg/kg/min) and norepinephrine (NE 3.2 μg/kg/min) stress to measure an index of MBF response. β-adrenergic specificity of NE was evaluated by pretreatment with α-adrenergic-antagonist phentolamine (PHE), and β2-selectivity was assessed using SB.

RESULTS: Adjusting for changes in heart rate × systolic blood pressure product (RPP), the same stress/rest MBF ratio of 1.4 was measured using low-dose SB and NE in normal mice (equivalent to human CPT response). The MBF response was correlated with changes in MVO2 (p = 0.02). Nitric oxide synthase (NOS)-inhibited mice (N(g)-nitro-L-arginine methyl ester (L-NAME) pretreatment and endothelial nitric oxide synthase (eNOS) knockout) were used to assess the EFRNOM, in which the low-dose SB- and NE-stress MBF responses were completely blocked (p = 0.02). With high-dose SB-stress, the MBF ratio was reduced by 0.4 following NOS inhibition (p = 0.03).

CONCLUSIONS: Low-dose salbutamol β2-adrenergic-stress [(11)C]acetate micro-PET imaging can be used to measure coronary-specific EFRNOM in mice and may be suitable for assessment of endothelial dysfunction in small animal models of disease and evaluation of new therapies.

Keywords: Adrenergic receptor; Endothelial function; Myocardial blood flow; Vascular reactivity sympathetic nervous system; Vasodilatation

References

  1. Am J Physiol. 1989 Sep;257(3 Pt 1):E309-17 - PubMed
  2. Fundam Clin Pharmacol. 2011 Jun;25(3):333-42 - PubMed
  3. J Am Coll Cardiol. 1991 Jun;17(7):1461-70 - PubMed
  4. Am J Physiol Heart Circ Physiol. 2003 Feb;284(2):H501-10 - PubMed
  5. Am J Ther. 1997 Jan;4(1):34-8 - PubMed
  6. Circ Res. 1993 Aug;73(2):252-63 - PubMed
  7. Eur J Nucl Med Mol Imaging. 2007 Nov;34(11):1765-74 - PubMed
  8. Circulation. 2005 Jan 25;111(3):288-94 - PubMed
  9. J Nucl Med. 2006 Mar;47(3):477-85 - PubMed
  10. Exerc Sport Sci Rev. 2012 Jan;40(1):37-42 - PubMed
  11. Eur J Nucl Med Mol Imaging. 2007 Jan;34(1):20-7 - PubMed
  12. Eur Respir J. 1991 May;4(5):544-50 - PubMed
  13. Circulation. 2002 Jul 30;106(5):550-5 - PubMed
  14. J Nucl Med. 2001 Aug;42(8):1174-82 - PubMed
  15. Pathophysiology. 2008 Jun;15(1):49-67 - PubMed
  16. J Physiol. 2013 Jun 1;591(11):2937-47 - PubMed
  17. Am J Physiol. 1996 Jul;271(1 Pt 2):H59-67 - PubMed
  18. Eur J Nucl Med. 2001 Mar;28(3):334-9 - PubMed
  19. J Cardiovasc Electrophysiol. 2004 Mar;15(3):316-22 - PubMed
  20. J Nucl Cardiol. 2010 Apr;17 (2):264-75 - PubMed
  21. J Nucl Cardiol. 2012 Oct;19(5):979-86 - PubMed
  22. J Am Coll Cardiol. 2005 May 3;45(9):1505-12 - PubMed
  23. Vet Anaesth Analg. 2007 Nov;34(6):377-87 - PubMed
  24. Nucl Med Commun. 2012 Sep;33(9):917-25 - PubMed
  25. Am J Cardiol. 1996 Sep 1;78(5):526-31 - PubMed
  26. Antioxid Redox Signal. 2008 Sep;10(9):1631-74 - PubMed
  27. Endothelium. 2008 Jul-Aug;15(4):157-63 - PubMed
  28. J Physiol. 2010 May 1;588(Pt 9):1515-25 - PubMed
  29. Heart. 2009 Apr;95(7):603-8 - PubMed
  30. J Hum Hypertens. 2004 Jun;18(6):445-52 - PubMed
  31. J Nucl Cardiol. 2010 Aug;17 (4):600-16 - PubMed
  32. J Nucl Med. 2013 Sep;54(9):1637-44 - PubMed
  33. Eur J Nucl Med Mol Imaging. 2010 Dec;37(12 ):2233-41 - PubMed
  34. Eur Heart J. 2012 Feb;33(4):495-504 - PubMed
  35. J Am Soc Echocardiogr. 2012 Aug;25(8):911-8 - PubMed
  36. J Cereb Blood Flow Metab. 1998 Jul;18(7):716-23 - PubMed
  37. Clin Physiol Funct Imaging. 2010 Jul;30(4):279-84 - PubMed

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