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Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute

Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute University of Calgary. Disclosures. Department of Cardiac Sciences and Libin Cardiovascular Institute – U of Calgary Grant support by Alberta Innovates Merck, Amgen, Abbott. BASELINE (3.65 mm).

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Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute

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  1. Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute University of Calgary

  2. Disclosures • Department of Cardiac Sciences and Libin Cardiovascular Institute – U of Calgary • Grant support by Alberta Innovates • Merck, Amgen, Abbott

  3. BASELINE (3.65 mm) REACTIVE HYPEREMIA (4.08 mm) Flow-Mediated Vasodilation FMD = 10.5 %

  4. Microvasculature Philpott et al. ATVB 2007;27:2065

  5. Ischemic Conditioning • Ischemia-reperfusion injury • Kloner JCI 1974:54:1496 – No reflow in dogs • Reimer et al. Circulation 1977; 56:786 – wavefront of ischemic death • Braunwald and Kloner. JCI 1985;76:1713 – double edged sword and concept of stunned myocardium Circulation 1982 • Ischemic conditioning • Murry et al. Circulation 1986; 74:1174 – IPC

  6. Ischemic Conditioning Significant parallelism between pre and post-conditioning Vinten-Johansen JAP 2007;103:1441

  7. Ischemic Conditioning and Endothelial Function • Ischemia-reperfusion injury causes injury and acute conduit and NO dependent micro-vessel endothelial dysfunction • Pre and post-conditioning with IPC bouts of transient ischemia attenuate this abnormality • Pharmacological conditioning prevents IR endothelial dysfunction acutely but less reliably chronically • IPC improves LV function during acute myocardial infarction in some but not all studies • Remote IPC also results in variable outcomes • IPC may also have favorable effects on other outcomes including blood pressure

  8. Ischemic Conditioning Kharbanda Circ 2001; 103:1624

  9. Ischemic Conditioning Attenuation of NO dependent increases in FBF post IR injury with activation of neutrophils as well Attenuation of FMD with pre-conditioning attenuating this abnormality Kharbanda Circ 2001; 103:1624

  10. Remote Ischemic Conditioning 20 minutes of ischemia with and without 3 cycles of 5 minutes of IPC on the contra-lateral arm Kharbanda Circ 2002; 106:2881

  11. Remote Ischemic Post-Conditioning 19 healthy subjects RIPC and RPostC 20 minutes of ischemia With and without glibenclamide to assess K+ ATP channels Both prevented the ↓ FMD with IR (PostC in leg but not arm) and this was blocked by glibenclamide Loukogeorgakis et al. Circulation 2007;116:1386

  12. Ischemia-Reperfusion Injury 45 normal subjects with 15 minutes of ischemia Attenuation of FMD but no change in hyperemic stimulus or PAT-index IR doesn’t impair microvascular function Alhejily et al. Microcirculation 2013

  13. Pharmacologic Conditioning - Statins Liuni et al. Clin Hemorheol 2010;45:161

  14. Ischemic Conditioning 30 healthy subjects IR alone vs 1 day IPC vs 7 d IPC protocol 3 cycles of 5 min of ischemia and reperfusion Celecoxib did not change results. Both 1 and 7 days of IPC attenuated IR decrease in FMD Luca et al. JAHA 2013;2(1)

  15. Ischemic Conditioning 30 healthy subjects IR alone vs 1 day IPC vs 7 d IPC protocol 3 cycles of 5 min of ischemia and reperfusion Celecoxib did not change results. Both 1 and 7 days of IPC attenuated IR decrease in FMD Luca et al. JAHA 2013;2(1)

  16. Ischemic Conditioning and Endothelial Function • Effect of acute or repeated episodes of IPC in patients with endothelial dysfunction is unknown • Acute and 7 days of IPC can ameliorate the IR-induced decreases in FMD with no effect on measures of microvascular response (hyperemic velocity or PAT) • Pre-conditioning may be more effective than post-conditioning in the forearm acute endothelial dysfunction model (and studies are mixed with AMI) • Further studies are needed to assess the effects of longer term IPC on endothelial function and cardiovascular pathophysiology

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