Skip to main content

Advertisement

SpringerLink
Log in

Reduced baseline diameter and contraction of peripheral retinal arterioles immediately after remote ischemia in diabetic patients

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Remote ischemic conditioning (RIC) implies that transient ischemia in one organ can affect blood flow and protect from ischemia in another remote organ such as the retina. The purpose of the present study was to investigate the effect of RIC on the diameter of retinal arterioles in patients with diabetic retinopathy and whether this effect differs among peripheral and macular vessels.

Methods

In twenty type 1 diabetes patients aged 20–31 years, the Dynamic Vessel Analyzer (DVA) was used to measure diameters of peripheral and macular arterioles during rest, isometric exercise, and flicker stimulation. Measurements were obtained before, immediately after, and 1 h after RIC, and were compared to responses obtained from normal persons.

Results

The reduced baseline diameter (p < 0.009) and contraction of peripheral retinal arterioles during isometric exercise (p = 0.025) observed immediately after RIC in normal persons were absent in the studied diabetic patients.

Conclusions

RIC affects the diameter of peripheral but not macular arterioles in normal persons, but the response is abolished in diabetic patients.

Trial registration

NCT03906383

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Stitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, Jenkins A, Gardiner TA, Lyons TJ, Hammes H-P, Simó R, Lois N (2016) The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res 51:156–186

    PubMed  Google Scholar 

  2. Bek T (2009) Inner retinal ischaemia: current understanding and needs for further investigations. Acta Ophthalmol 87(4):362–367

    PubMed  Google Scholar 

  3. Bek T (2013) Regional morphology and pathophysiology of retinal vascular disease. Prog Retin Eye Res 36:247–259

    CAS  PubMed  Google Scholar 

  4. Jorgensen CM, Bek T (2017) Lack of differences in the regional variation of oxygen saturation in larger retinal vessels in diabetic maculopathy and proliferative diabetic retinopathy. Br J Ophthalmol 101(6):752–757

    PubMed  Google Scholar 

  5. Skov Jensen P, Jeppesen P, Bek T (2011) Differential diameter responses in macular and peripheral retinal arterioles may contribute to the regional distribution of diabetic retinopathy lesions. Graefes Arch Clin Exp Ophthalmol 249(3):407–412

    PubMed  Google Scholar 

  6. England TJ, Hedstrom A, O'Sullivan S, Donnelly R, Barrett DA, Sarmad S, Sprigg N, Bath PM (2017) RECAST (Remote Ischemic Conditioning After Stroke Trial): a pilot randomized placebo controlled phase II trial in acute ischemic stroke. Stroke 48(5):1412–1415

    PubMed  Google Scholar 

  7. Chong J, Bulluck H, Yap EP, Ho AF, Boisvert WA, Hausenloy DJ (2018) Remote ischemic conditioning in ST-segment elevation myocardial infarction—an update. Cond Med 1(5):13–22

    PubMed  PubMed Central  Google Scholar 

  8. Pickard JM, Botker HE, Crimi G, Davidson B, Davidson SM, Dutka D, Ferdinandy P, Ganske R, Garcia-Dorado D, Giricz Z, Gourine AV, Heusch G, Kharbanda R, Kleinbongard P, MacAllister R, McIntyre C, Meybohm P, Prunier F, Redington A, Robertson NJ, Suleiman MS, Vanezis A, Walsh S, Yellon DM, Hausenloy DJ (2015) Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop. Basic Res Cardiol 110(1):453

    PubMed  Google Scholar 

  9. El Dabagh Y, Petersen L, Pedersen M, Bek T (2017) The diameter of retinal vessels is affected by transient ischemia of the arm in normal persons. Invest Ophthalmol Vis Sci 58(12):5263–5269

    PubMed  Google Scholar 

  10. Garhofer G, Bek T, Boehm AG, Gherghel D, Grunwald J, Jeppesen P, Kergoat H, Kotliar K, Lanzl I, Lovasik JV, Nagel E, Vilser W, Orgul S, Schmetterer L (2010) Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol 88(7):717–722

    PubMed  Google Scholar 

  11. Bek T, Lund-Andersen H (1990) Accurate superimposition of perimetry data onto fundus photographs. Acta Ophthalmol 68/1:11–18

    Google Scholar 

  12. Johnsen J, Pryds K, Salman R, Lofgren B, Kristiansen SB, Botker HE (2016) The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection. Basic Res Cardiol 111(2):10

    PubMed  Google Scholar 

  13. Mehlsen J, Erlandsen M, Poulsen PL, Bek T (2012) Individualized optimization of the screening interval for diabetic retinopathy: a new model. Acta Ophthalmol 90(2):109–114

    PubMed  Google Scholar 

  14. Grauslund J, Andersen N, Andresen J, Flesner P, Haamann P, Heegaard S, Larsen M, Laugesen CS, Schielke K, Skov J, Bek T (2018) Evidence-based Danish guidelines for screening of diabetic retinopathy. Acta Ophthalmol 96(8):763–769

    CAS  PubMed  Google Scholar 

  15. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682

    CAS  PubMed  Google Scholar 

  16. Kleinbongard P, Skyschally A, Heusch G (2017) Cardioprotection by remote ischemic conditioning and its signal transduction. Pflugers Arch - Eur J Physiol 469(2):159–181

    CAS  Google Scholar 

  17. Lin J, Roth S (1999) Ischemic preconditioning attenuates hypoperfusion after retinal ischemia in rats. Invest Ophthalmol Vis Sci 40(12):2925–2931

    CAS  PubMed  Google Scholar 

  18. Shimizu M, Konstantinov IE, Kharbanda RK, Cheung MH, Redington AN (2007) Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs. Acta Physiol 190(2):103–109

    CAS  Google Scholar 

  19. Pedersen L, Jeppesen P, Knudsen ST, Poulsen PL, Bek T (2014) Improvement of mild retinopathy in type 2 diabetic patients correlates with narrowing of retinal arterioles. A prospective observational study. Graefes Arch Clin Exp Ophthalmol 252(10):1561–1567

    PubMed  Google Scholar 

  20. Bek T (2017) Diameter changes of retinal vessels in diabetic retinopathy. Curr Diab Rep 17(10):82

    PubMed  Google Scholar 

  21. Jeppesen P, Gregersen PA, Bek T (2004) The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer. Graefes Arch Clin Exp Ophthalmol 242(11):914–919

    PubMed  Google Scholar 

  22. Kristinsson JK, Gottfredsdottir MS, Stefansson E (1997) Retinal vessel dilatation and elongation precedes diabetic macular oedema. Br J Ophthalmol 81(4):274–278

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tilma KK, Bek T (2012) Topical treatment for 1 week with latanoprost but not diclofenac reduces the diameter of dilated retinal arterioles in patients with type 1 diabetes mellitus and mild retinopathy. Acta Ophthalmol 90(8):750–755

    CAS  PubMed  Google Scholar 

  24. Pemp B, Cherecheanu AP, Garhofer G, Schmetterer L (2013) Calculation of central retinal artery diameters from non-invasive ocular haemodynamic measurements in type 1 diabetes patients. Acta Ophthalmol 91(5):e348–e352

    PubMed  Google Scholar 

  25. Frederiksen CA, Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Bek T (2006) The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy. Graefes Arch Clin Exp Ophthalmol 244(10):1255–1261

    PubMed  Google Scholar 

  26. Wider J, Przyklenk K (2014) Ischemic conditioning: the challenge of protecting the diabetic heart. Cardiovasc Diagn Ther 4(5):383–396

    PubMed  PubMed Central  Google Scholar 

  27. Jeppesen P, Knudsen ST, Poulsen PL, Hessellund A, Schmitz O, Bek T (2013) Acute hyperinsulinemia increases the contraction of retinal arterioles induced by elevated blood pressure. Am J Physiol Heart Circ Physiol 305(11):H1600–H1604

    CAS  PubMed  Google Scholar 

  28. Jensen RV, Stottrup NB, Kristiansen SB, Botker HE (2012) Release of a humoral circulating cardioprotective factor by remote ischemic preconditioning is dependent on preserved neural pathways in diabetic patients. Basic Res Cardiol 107(5):285

    PubMed  Google Scholar 

  29. Lejay A, Fang F, John R, Van JA, Barr M, Thaveau F, Chakfe N, Geny B, Scholey JW (2016) Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus. J Mol Cell Cardiol 91:11–22

    CAS  PubMed  Google Scholar 

  30. Przyklenk K, Maynard M, Greiner DL, Whittaker P (2011) Cardioprotection with postconditioning: loss of efficacy in murine models of type-2 and type-1 diabetes. Antioxid Redox Signal 14(5):781–780

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Jensen RV, Zachara NE, Nielsen PH, Kimose HH, Kristiansen SB, Bøtker HE (2013) Impact of O-GlcNAc on cardioprotection by remote ischaemic preconditioning in non-diabetic and diabetic patients. Cardiovasc Res 97(2):369–378

    CAS  PubMed  Google Scholar 

  32. Jensen PS, Aalkjaer C, Bek T (2018) The vasodilating effect of glucose differs among vessels at different branching level in the porcine retina ex vivo. Exp Eye Res 179:150–156

    PubMed  Google Scholar 

  33. Skov Jensen P, Metz Mariendal Pedersen S, Aalkjaer C, Bek T (2016) The vasodilating effects of insulin and lactate are increased in precapillary arterioles in the porcine retina ex vivo. Acta Ophthalmol 94(5):454–462

    CAS  PubMed  Google Scholar 

  34. Blum M, Pils C, Muller UA, Strobel J (2006) The myogenic response of retinal arterioles in diabetic retinopathy. Ophthalmologe 103(3):209–213

    CAS  PubMed  Google Scholar 

  35. Petersen L, Bek T (2016) The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis. Graefes Arch Clin Exp Ophthalmol 254(12):2339–2346

    CAS  PubMed  Google Scholar 

  36. Petersen L, Bek T (2016) Preserved pressure autoregulation but disturbed cyclo-oxygenase and nitric oxide effects on retinal arterioles during acute hypoxia in diabetic patients without retinopathy. Ophthalmologica 235(2):114–120

    CAS  PubMed  Google Scholar 

  37. Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116(4):674–699

    CAS  PubMed  Google Scholar 

  38. Hausenloy DJ, Yellon DM (2010) The second window of preconditioning (SWOP) where are we now? Cardiovasc Drugs Ther 24(3):235–254

    PubMed  Google Scholar 

  39. Zhou K, Yang B, Zhou XM, Tan CM, Zhao Y, Huang C, Liao XB, Xiao HB (2007) Effects of remote ischemic preconditioning on the flow pattern of the left anterior descending coronary artery in normal subjects. Int J Cardiol 122(3):250–251

    PubMed  Google Scholar 

  40. Robert R, Vinet M, Jamet A, Coudroy R (2017) Effect of non-invasive remote ischemic preconditioning on intra-renal perfusion in volunteers. J Nephrol 30(3):393–395

    CAS  PubMed  Google Scholar 

  41. Kolbenschlag J, Sogorski A, Kapalschinski N, Harati K, Lehnhardt M, Daigeler A, Hirsch T, Goertz O (2016) Remote ischemic conditioning improves blood flow and oxygen saturation in pedicled and free surgical flaps. Plast Reconstr Surg 138(5):1089–1097

    CAS  PubMed  Google Scholar 

  42. Randhawa PK, Jaggi AS (2016) Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection. Life Sci 155:140–146

    CAS  PubMed  Google Scholar 

  43. Riis-Vestergaard MJ, Misfeldt MW, Bek T (2014) Dual Effects of adenosine on the tone of porcine retinal arterioles in vitro adenosine effects on porcine retinal arteriole tone. Invest Ophthalmol Vis Sci 55(3):1630–1636

    CAS  PubMed  Google Scholar 

  44. Hein TW, Yuan Z, Rosa JRH, Kuo L (2005) Requisite roles of A2A receptors, nitric oxide, and KATP channels in retinal arteriolar dilation in response to adenosine. Invest Ophthalmol Vis Sci 46(6):2113–2119

    PubMed  Google Scholar 

Download references

Funding

The study was funded by the Fight for Sight Foundation and Jochum Jensens Foundation.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Aarhus University Hospital, 8200, Aarhus N, Denmark

    Yasmin El Dabagh, Line Petersen & Toke Bek

  2. Comparative Medicine Laboratory, Department of Clinical Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark

    Yasmin El Dabagh & Michael Pedersen

Authors
  1. Yasmin El Dabagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Line Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toke Bek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasmin El Dabagh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the Regional Committee for Scientific Ethics (De Videnskabsetiske Komitéer, 1-10-72-112-17) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El Dabagh, Y., Petersen, L., Pedersen, M. et al. Reduced baseline diameter and contraction of peripheral retinal arterioles immediately after remote ischemia in diabetic patients. Graefes Arch Clin Exp Ophthalmol 257, 2095–2101 (2019). https://doi.org/10.1007/s00417-019-04407-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-019-04407-x

Keywords

Search

Navigation