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Small arteries

Mechanistic insights into the relationship between wave reflection and retinal artery flow pulsatility . McDonnell BJ *, Coulson J **, Zagura M***, Munnery I **, Munnery M **, Stohr E*, Shave R*, McEniery CM ¶ , Wilkinson IB ¶ , Cockcroft JR**. *University of Wales Institute, Cardiff.

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Small arteries

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  1. Mechanistic insights into the relationship between wave reflection and retinal artery flow pulsatility. McDonnell BJ *, Coulson J **, Zagura M***, Munnery I **, Munnery M **, Stohr E*, Shave R*, McEniery CM ¶, Wilkinson IB ¶, Cockcroft JR**. *University of Wales Institute, Cardiff. **Wales Heart Research Institute, Heath Hospital, Cardiff. ***University of Tartu, Tartu, Estonia. ¶Department of Clinical Pharmacology, Addenbrooke’s Hospital, Cambridge.

  2. Pulsatile to smooth flow/pressure in the arterial system 120 80 Blood Pressure (mmHg) Large arteries Small arteries Arterioles Capillaries Veins

  3. Large artery stiffness and microvascular damage Increased Large artery stiffness Increased Pulsatility (PP) High PP transmitted to micro-circulation Increased damage to end organs

  4. Decline in GFR is More Closely Related to Pulse Pressure than MAP Fesler et al. J Hypertens 2007;25:1796

  5. Age-related Macular Degeneration is Associated with Increased Central Pressure Sato et al. Graefe’s Arch Clin Exp Opthalmol. 2006;244:963

  6. What are the determinants of pulsatility????

  7. Determinants of pulsatility Q: AIx? -The degree to which the incident wave is reflected?? Large Artery Stiffness Systolic Pressure Diastolic Pressure Stroke Volume Physiology, Berne and Levy

  8. Large artery stiffness and microvascular damage Increased Large artery stiffness Increased Pulsatility (PP) High PP transmitted to micro-circulation Increased damage to end organs

  9. Large artery stiffness and microvascular damage Increased Large artery stiffness AIx Increased Pulsatility (PP) Decrease PP transmitted to micro-circulation Decreased damage to end organs

  10. Relationship between Pulse Pressure and Wave Reflection on retinal artery Pulsatility Ratio N=64

  11. Difference in PR between highest and lowest of AIx.

  12. An increased AIx may have a potentially beneficial effect in reflecting an otherwise high pulsatile flow wave travelling to the micro-circulation

  13. Step 2: Aim of study: • To investigate if wave reflection is directly related to degree of pulsatility in the retinal artery. • By reducing/manipulating wave reflection via administration of sublingual GTN.

  14. The Effects of GTN

  15. Methods • Participants: • 9 individuals, aged 63±6 years (3 Males, 6 Females) • -free from CVD and ocular disease • and free from taking sympathomimetic compounds. • Vascular Measurements: • (Peripheral and Central BP and HR, (using Mobilograph, IEM) • CBP and AIx (using SphygmoCor) • Retinal Artery Flow Measurements: • (PI using Doppler Ultrasound, GE).

  16. Measuring of flow oscillations in the retinal artery using: • Pulsatility Index as a measure of flow wave pulsatility. PI takes into account Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV) of the flow wave, whilst accounting for Mean Flow Velocity (MV).

  17. Doppler ultrasound to measure arterial blood flow in the retinal artery Pulsatility Index: PI = (PSV/EDV) / MV PSV EDV Mv

  18. GTN Protocol All measurements were recorded simultaneously at: Baseline ADMINISTRATION OF 500µg of GTN 1min 3min 5min 10min 15mins

  19. Results

  20. P<0.05

  21. Relationship between AIx and PI

  22. Summary Evidence suggesting a direct inverse relationship between changes in Wave Reflection and changes in flow Pulsatility in the retinal artery.

  23. Conclusion Wave reflection may have a protective effect on the pulsatile flow wave transmitted to the microvasculature.

  24. Acknowledgements: • Prof John Cockcroft • Mrs Margaret Munnery • Dr James Coulson • Mr Iain Munnery • Maksim Zagura Wales Heart Research Institute, Heath Hospital, Cardiff: Vascular Research Unit, Addenbrooke’s Hospital, Cambridge: • Dr Ian Wilkinson • Dr Carmel McEniery • Dr Kaisa Maki-Petaja

  25. Effects of Antihypertensive Drugs on Central Pressure, Wave Reflection and Aortic PWV McEniery CM. CurrHypertens Rep. 2009;11:253-9

  26. High PWV with High Wave Reflection = Low Pulsatility in Microcirculation

  27. High PWV with Low Wave Reflection = HIGH Pulsatility in Microcirculation

  28. Effect of aortic stiffness on retinal artery Pulsatility Ratio

  29. Percentage change in PI and AIx from baseline

  30. * * P<0.05

  31. Effect of aPWV and AIx on the microvasculature Elastic Segment Muscular Segment Macrocirculation Microcirculation

  32. Effect of aPWV and AIx on the microvasculature Elastic Segment Muscular Segment Macrocirculation Microcirculation

  33. Effect of aPWV and AIx on the microvasculature Elastic Segment Muscular Segment Macrocirculation Microcirculation

  34. Aims and objectives: • To determine the relationship between aPWV, AIx and pulsatility in the retinal artery. • To investigate whether individuals with highPWV’s and low AIxhave higher pulsatility in the microcirculation than individuals with low PWV’sand high AIx.

  35. Aims and objectives: • To determine the relationship between aPWV, AIx and pulsatility in the retinal artery.

  36. Microvascular damage ↑ MAP ↑ PP Large vessel stiffening

  37. Increased PWV was associated with increased microalbuminuria in the general population Hoorn study

  38. Methods Participants: • 62 individuals, aged 39-83 years • free from CVD and ocular disease • and free from taking sympathomimetic compounds. • Macrovascular measurements: • Peripheral and Central BP • Augmentation Index (SphygmoCor) • Aortic PWV (carotid – femoral) (SphygmoCor) • Microvascular measurements: • Retinal Artery Pulsatility Ratio (PR) • Retinal Artery Resistance Index (RI) (Retinal Artery Doppler Ultrasound)

  39. Methods IIDoppler ultrasound to measure arterial blood flow in the retinal artery Pulsatility Index: PI = (PSV/EDV) / mean flow velocity Resistance index: RI = (Peak systolic velocity- End diastolic velocity)/Peak systolic velocity Peak Systolic Velocity End Diastolic Velocity Taken from Baxter et al. Opthalmol. Vis. Sci.1992

  40. Results

  41. Summary • Significant relationship between increased CF PWV and increased pulsatility in the retinal artery. • Increased wave reflection was inversely related to increased pulsatility in the retinal artery. • Individuals with high PWV and low AIx had significantly higher pulsatility in the retinal artery compared to individuals with low PWV and high AIx.

  42. Future ResearchEffects of Atenolol on PI and AIx??????

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