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Post-conditioning the human heart to reduce infarct size

Post-conditioning the human heart to reduce infarct size. Michel OVIZE Inserm E 0226 and Cardiology Hospital Lyon France. Acute Myocardial Infarction. common (  500 000 / year in USA) affects outcome : mortality disabling: heart failure. Infarct size is a determinant of mortality.

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Post-conditioning the human heart to reduce infarct size

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  1. Post-conditioning the human heart to reduce infarct size Michel OVIZE Inserm E 0226 and Cardiology Hospital Lyon France

  2. Acute Myocardial Infarction • common ( 500 000 / year in USA) • affects outcome : mortality • disabling: heart failure

  3. Infarct size is a determinant of mortality Gibbons et al. JACC 2004;44:1533-1542

  4. Reperfusion improves outcome van Domburg et al. JACC2005:15–20

  5. stunning : accepted • arrhythmias : accepted • no-reflow : accepted • necrosis : debated Reperfusion Injury «a double edged sword»

  6. 35 30 25 * * 20 control (% of tissue area) PostC 15 PreC 10 5 0 AR/LV AN/AR Postconditioning Zhao ZQ et al. Am J Physiol 2003

  7. Ischemia Reperfusion reperfusion injury Infarct size ischemic injury time coronary occlusion PreC Postconditioning Infarction: a two-component damage

  8. Current treatment of AMI • -blockers • ACE inhibitors • statins • …. improve post-MI outcome, but not via a reduction in infarct size • Ischemic damage : YES • thrombolysis / PCI ischemia time • antiplatelet agents ischemia time • Reperfusion damage : NO Action on infarct size

  9. Loosing protection A narrow time window

  10. Does Postconditioning protect the human heart ? A « proof of concept » study

  11. Study population A « Human Model » of Postconditioning • Inclusion criteria • Age ≥ 18 • First acute (STE)MI / chest pain onset < 6 hrs • Need for emergency PTCA • Exclusion criteria • Cardiac arrest • Cardiogenic shock • Circumflex coronary artery as culprit for AMI

  12. Experimental Design Eligible Patient TIMI 0 Collat = 0 Coronary + LV Angio Informed consent Randomization Angioplasty reperf. TIMI > 2

  13. Occluded coronary artery Reperfusion Control Direct stenting 1’ 1’ 1’ 1’ Postcond 1’ 1’ 1’ 1’ Balloon inflations - deflations Post-Conditioning algorythm Staat et al. Circulation. 2005;112:2143-2148

  14. Study Endpoints • Total CK release over first 72 hrs of reperfusion • every 4 hr on Day 1 • every 6 hr on Day 2 • every 8 hr on Day 3

  15. Results

  16. Study population - baseline characteristics

  17. Length of the Abnormally Contracting Segments of the LVED endocardial perimeter Length of the LVED endocardial perimeter LV End Diastole A B LV End Systole B - C A - D D C Area at Risk estimation on LV angiogram Anterior infarct ACS = X 100 %

  18. (%) 50 ns min. 500 40 ns 400 30 300 20 control PostC 200 PostC control Determinants of infarct size Area at Risk size (ACS) Duration of Ischemia

  19. Control Post-Cond CK release during reperfusion 5000 4000 - 36 % (p < 0.05) 3000 CK release (AUC: arbitrary units) 2000 1000 0 4h 8h 24h 48h 72h Adm. Reperfusion PTCA Staat et al. Circulation. 2005;112:2143-2148

  20. 9.105 8. 105 7.105 Control 6.105 5.105 PostC CK release (AUC) 4.105 3.105 2.105 1.105 0 0 20 40 60 ACS (%) CK release versus ACS (infarct size versus area at risk)

  21. 3 * 3 2,5 2 2 Blush grade ST segment shift (mm) 1,5 1 1 0,5 0 0 PostC PostC C C Estimation of « no reflow » Staat et al. Circulation. 2005;112:2143-2148

  22. Toward New Clinical Strategies Ischemic PostC PCI - thrombolysis Pharmaco PostC adenosine, NO, K+ATP openers survival kinases mPTP inhibitors, ….. drug

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