Advertisement

Journal of Nuclear Cardiology

, Volume 25, Issue 3, pp 887–896 | Cite as

Effect of remote ischemic conditioning on myocardial perfusion in patients with suspected ischemic coronary artery disease

  • Kasper Pryds
  • Roni Ranghøj Nielsen
  • Camilla Molich Hoff
  • Lars Poulsen Tolbod
  • Kirsten Bouchelouche
  • Jing Li
  • Michael Rahbek Schmidt
  • Andrew N. Redington
  • Jørgen Frøkiær
  • Hans Erik Bøtker
Original Article

Abstract

Background

Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury and may modulate coronary blood flow. We investigated whether RIC affects resting myocardial perfusion (MP) in patients with suspected ischemic coronary artery disease by quantitative MP imaging.

Methods and Results

We included 49 patients with suspected ischemic coronary artery disease. Resting MP was quantified by 82Rubidium positron emission tomography/computed tomography (82Rb-PET/CT) imaging before and after RIC, performed as four cycles of 5 minutes upper arm ischemia and reperfusion. Subsequent adenosine 82Rb-PET/CT stress-imaging identified non-ischemic and reversibly ischemic myocardial segments. MicroRNA-144 plasma levels were measured before and after RIC. Normalized for rate pressure product, RIC did not affect MP globally (P = .64) or in non-ischemic myocardial segments (P = .58) but decreased MP in reversibly ischemic myocardial segments (−0.11 mL/min/g decrease in MP following RIC; 95% CI −0.17 to −0.06, P < .001). However, we found no effect of RIC when MP was normalized for cardiac work. MicroRNA-144 plasma levels increased following RIC (P = .006) but did not correlate with a change in global MP in response to RIC (P = .40).

Conclusions

RIC did not substantially affect resting MP globally or in non-ischemic and reversibly ischemic myocardial territories in patients with suspected ischemic coronary artery disease.

Keywords

82Rb-PET/CT positron emission tomography/computed tomography ischemic heart disease myocardial perfusion remote ischemic conditioning ischemic preconditioning microRNA-144 

Abbreviations

82Rb-PET/CT

82Rubidium positron emission tomography/computed tomography

CI

Confidence interval

MFR

Myocardial flow reserve

MP

Myocardial perfusion

MVR

Myocardial vascular resistance

RIC

Remote ischemic conditioning

RPP

Rate pressure product

Notes

Acknowledgement

The authors thank the staff from Department of Nuclear Medicine, Aarhus University Hospital and Casper Carlsen Elkjær and Anja Helveg Larsen for excellent administrative and technical assistance.

Disclosure

MRS and HEB are shareholders in CellAegis Devices Inc. ANR is member of the Scientific Advisory Board of CellAegis Devices Inc. KP, RRN, CMH, KB, JL and JF report no potential conflict of interest.

Supplementary material

12350_2016_709_MOESM1_ESM.pptx (346 kb)
(pptx 347 kb)

References

  1. 1.
    Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol 2015;65:177–95.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Heusch G. Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 2015;116:674–99.CrossRefPubMedGoogle Scholar
  3. 3.
    Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 2002;106:2881–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Heusch G. The coronary circulation as a target of cardioprotection. Circ Res 2016;118:1643–58.CrossRefPubMedGoogle Scholar
  5. 5.
    Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genom 2004;19:143–50.CrossRefGoogle Scholar
  6. 6.
    Shimizu M, Konstantinov IE, Kharbanda RK, Cheung MH, Redington AN. Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs. Acta Physiol (Oxf) 2007;190:103–9.CrossRefGoogle Scholar
  7. 7.
    Zhou K, Yang B, Zhou XM, Tan CM, Zhao Y, Huang C, et al. Effects of remote ischemic preconditioning on the flow pattern of the left anterior descending coronary artery in normal subjects. Int J Cardiol 2007;122:250–1.CrossRefPubMedGoogle Scholar
  8. 8.
    Kono Y, Fukuda S, Hanatani A, Nakanishi K, Otsuka K, Taguchi H, et al. Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure. Drug Design Dev Therapy 2014;8:1175–81.Google Scholar
  9. 9.
    Li J, Rohailla S, Gelber N, Rutka J, Sabah N, Gladstone RA, et al. MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Res Cardiol 2014;109:423.CrossRefPubMedGoogle Scholar
  10. 10.
    Lortie M, Beanlands RS, Yoshinaga K, Klein R, Dasilva JN, DeKemp RA. Quantification of myocardial blood flow with 82Rb dynamic PET imaging. Eur J Nucl Med Mol Imaging 2007;34:1765–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Harms HJ, Knaapen P, de Haan S, Halbmeijer R, Lammertsma AA, Lubberink M. Automatic generation of absolute myocardial blood flow images using [15O]H2O and a clinical PET/CT scanner. Eur J Nucl Med Mol Imaging 2011;38:930–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    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.CrossRefPubMedGoogle Scholar
  13. 13.
    Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539–42.CrossRefPubMedGoogle Scholar
  14. 14.
    Van Tosh A, Votaw JR, Reichek N, Palestro CJ, Nichols KJ. The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated Rb-82 PET myocardial perfusion imaging. J Nucl Cardiol 2013;20:1060–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Naya M, Murthy VL, Taqueti VR, Foster CR, Klein J, Garber M, et al. Preserved coronary flow reserve effectively excludes high-risk coronary artery disease on angiography. J Nucl Med 2014;55:248–55.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Spinelli L, Petretta M, Acampa W, He W, Petretta A, Bonaduce D, et al. Prognostic value of combined assessment of regional left ventricular function and myocardial perfusion by dobutamine and rest gated SPECT in patients with uncomplicated acute myocardial infarction. J Nucl Med 2003;44:1023–9.PubMedGoogle Scholar
  17. 17.
    von Ziegler F, Brendel M, Uebleis C, Helbig S, Greif M, Ruemmler J, et al. SPECT myocardial perfusion imaging as an adjunct to coronary calcium score for the detection of hemodynamically significant coronary artery stenosis. BMC Cardiovasc Disor 2012;12:1.CrossRefGoogle Scholar
  18. 18.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001;25:402–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Efseaff M, Klein R, Ziadi MC, Beanlands RS, deKemp RA. Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging. J Nucl Cardiol 2012;19:997–1006.CrossRefPubMedGoogle Scholar
  20. 20.
    Hoole SP, Heck PM, White PA, Khan SN, O’Sullivan M, Clarke SC, et al. Remote ischemic preconditioning stimulus does not reduce microvascular resistance or improve myocardial blood flow in patients undergoing elective percutaneous coronary intervention. Angiology 2009;60:403–11.CrossRefPubMedGoogle Scholar
  21. 21.
    Salerno M, Beller GA. Noninvasive assessment of myocardial perfusion. Circ Cardiovasc Imaging 2009;2:412–24.CrossRefPubMedGoogle Scholar
  22. 22.
    Ramanathan T, Skinner H. Coronary blood flow. Contin Educ Anaesth Crit Care Pain 2005;5:61–4.CrossRefGoogle Scholar
  23. 23.
    Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 1990;66:913–31.CrossRefPubMedGoogle Scholar
  24. 24.
    Johnsen J, Pryds K, Salman R, Lofgren B, Kristiansen SB, Botker HE. The remote ischemic preconditioning algorithm: Effect of number of cycles, cycle duration and effector organ mass on efficacy of protection. Basic Res Cardiol 2016;111:10.CrossRefPubMedGoogle Scholar
  25. 25.
    Prior JO, Allenbach G, Valenta I, Kosinski M, Burger C, Verdun FR, et al. Quantification of myocardial blood flow with 82Rb positron emission tomography: Clinical validation with 15O-water. Eur J Nucl Med Mol Imaging 2012;39:1037–47.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Saraste A, Kajander S, Han C, Nesterov SV, Knuuti J. PET: Is myocardial flow quantification a clinical reality? J Nucl Cardiol 2012;19:1044–59.CrossRefPubMedGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2016

Authors and Affiliations

  • Kasper Pryds
    • 1
    • 2
  • Roni Ranghøj Nielsen
    • 1
  • Camilla Molich Hoff
    • 3
  • Lars Poulsen Tolbod
    • 3
  • Kirsten Bouchelouche
    • 3
  • Jing Li
    • 4
  • Michael Rahbek Schmidt
    • 1
  • Andrew N. Redington
    • 5
  • Jørgen Frøkiær
    • 3
  • Hans Erik Bøtker
    • 1
  1. 1.Department of CardiologyAarhus University HospitalAarhus NDenmark
  2. 2.Department of Clinical MedicineAarhus UniversityAarhus NDenmark
  3. 3.Department of Nuclear Medicine & PET CentreAarhus University HospitalAarhus NDenmark
  4. 4.Division of Cardiology, Labatt Family Heart CenterHospital for Sick ChildrenTorontoCanada
  5. 5.Heart InstituteUniversity of CincinnatiCincinnatiUSA

Personalised recommendations