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David R. Holmes, MD, FACC

David R. Holmes, MD, FACC. Autonomic Tone and Endothelial Effects. “It’s an experimental procedure. Every time you blow your nose, you’ll clear out your arteries!”. Plethysmography. Analogous to IABP Increases diastolic coronary pressure (and flow) Reduces myocardial O 2 demand

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David R. Holmes, MD, FACC

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  1. David R. Holmes, MD, FACC Autonomic Tone and Endothelial Effects

  2. “It’s an experimental procedure.Every time you blow your nose,you’ll clear out your arteries!”

  3. Plethysmography • Analogous to IABP • Increases diastolic coronary pressure (and flow) • Reduces myocardial O2 demand • Increases venous return • Increases cardiac output CM855921-3

  4. Doppler Echo of Descending Aorta • In aorta • Improved retrogradediastolic and enhanced antegrade systolic flow • Improved flow demonstrated in • Renal arteries • Carotid arteries • Internal mammary arteries • Coronary arteries Control EECP CM855921-4

  5. Intracoronary Doppler Flow EECP 1:2 (another patient) Baseline EECP 1:1 Michaels AD, et al. Circulation 2002; 106: 1237-42.

  6. ? ? ? ? EECP - Suggested Mechanisms Neovascularization  Endothelial Function  Clinical Benefit Peripheral effects Placebo effect

  7. NO PGI2 ET-1 AngII “EndothelialBalance” Normal Endothelial Function NO Function Vasodilatory Antithrombotic Antiproliferative Anti-inflammatory Vasodilation Atheroprotective

  8. ET-1 AngII NO PGI2 ET-1 AngII NO PGI2 “Endothelial Balance” Normal Endothelial Function Endothelial Dysfunction Vasoconstriction Atherogenic Vasodilation Atheroprotective

  9. NS Exercise thallium Normal Abnormal 400 P<0.005 Coronaryblood flowresponse(%) 300 P<0.01 200 100 0 Endothelial Dysfunction and Myocardial Ischemia Zeiher, Circulation 1995;91:2345-52. CP990350-5

  10. Flow-dependent dilation >19% 11-19% Event-freesurvival(%) Months Endothelial Dysfunction and Prognosis <11% Circulation 2000;101:1899-906.

  11. External CounterpulsationRandomized Study - NO Production P<0.001 *p<0.05 * P<0.05 * * Normal Pre- 6wk Pre- 1hr 2wk 4wk 6wk Qian, Int’l Cong Hrt Dz 1999

  12. Effect of Drugs and EECP on Plasma NO Levels * p < 0.05 vs Normals † p < 0.001 vs Pre-Drug ‡ p < 0.001 vs Pre-EECP ‡ ‡ ‡ ‡ † * * J Heart Dis 1999;1:193.

  13. Effect of EECP on Plasma NO Levels 43 patients with CAD † † * * * * p < 0.05; † p <0.01 vs Pre-EECP Circulation 1999;100(Suppl):I-832.

  14. Effect of EECP on Plasma ET-1 Levels 43 patients with CAD * * * † † * p < 0.05; † p <0.01 vs Pre-EECP Circulation 1999;100(Suppl):I-832.

  15. Enhanced External Counterpulsation (EECP) Improves Endothelial Function in Patients with Coronary Artery Disease Piero O. Bonetti, Gregory W. Barsness, Paul C. Keelan, Theresa I. Schnell, Geralyn M. Pumper, David R. Holmes Jr., Stuart T. Higano, Amir Lerman Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.

  16. PAT and Endothelial Function • Digital pulse volume depends on various factors including endothelium-dependent factors. • Reactive hyperemia (RH) is partly mediated by endothelium-derived nitric oxide. • RH-induced changes in digital pulse volume reflect endothelium-dependent vasoreactivity. • The combination of RH and PAT (RH-PAT) provides • a noninvasive test to assess endothelial function of • the peripheral microvasculature.

  17. Peripheral Arterial Tonometry (PAT)

  18. Post-occlusion PAT-amplitude RH-PAT index = Pre-occlusion PAT-amplitude Quantitation of RH-PAT (RH-PAT index)

  19. Occlusion RH-PAT protocol Cuffinflation 60 mm > SBP Cuff deflation 10 minutes 5 minutes 10 minutes

  20. Study Patients • 23 patients with established CAD and refractory angina not amenable to PCI or CABG • Exclusion criteria: - digital deformities • - allergy to latex • Standard 35-hour course of EECP over 7 weeks • CV medication unchanged during the study

  21. Study Protocol RH-PAT before + after EECP RH-PAT Day 1 Day 17 Day 35 1 Month EECP Follow-up CCS class Duke Activity Status Index (DASI)

  22. Patient Characteristics I

  23. Patient Characteristics II

  24. EECP and CCS class * p < 0.05 vs. day 1

  25. EECP and DASI * p < 0.05 vs. day 1

  26. EECP and Clinical Benefit CCS class DASI score No CCS- No DASI- Improvement Improvement 26% 26% DASI- CCS- Improvement Improvement 74% 74%

  27. Pre-EECP Post-EECP Acute Effect of EECP on Endothelial Function * p < 0.05

  28. Pre-EECP Post-EECP Acute Effect of EECP on Endothelial Function *p < 0.05

  29. 1.3 Pre-EECP Post-EECP Acute Effect of EECP on Endothelial Function * p < 0.05

  30. Pre-EECP Mid-term Effect of EECP on Endothelial Function

  31. Pre-EECP Mid-term Effect of EECP on Endothelial Function * p < 0.05 vs. days 1, 17, and 35 *

  32. Clinical Benefit and RH-PAT index - CCS class * p < 0.05 vs. day 1 * Day 1 1-month follow-up

  33. Clinical Benefit and RH-PAT index - DASI * p < 0.05 vs. day 1 * Day 1 1-month follow-up

  34. Summary • EECP acutely improves peripheral endothelial function in patients with advanced CAD. • Patients who experience clinical improvement in response to EECP show an additional enhancement of peripheral endothelial function 1 month after termination of EECP treatment.

  35. End of David R. Holmes, MD, FACCPresentation

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