1 / 22

Role of Adenosine in Acute Myocardial Infarction

Role of Adenosine in Acute Myocardial Infarction. Presented by: Mervyn B. Forman, MD, PhD, FACC. Potential Sequelae of Reperfusion on Ischemic Myocardium. Reperfusion Injury Conversion of reversibly injured endothelial and myocardial cells to irreversibly injured cells Myocardial Stunning

caine
Download Presentation

Role of Adenosine in Acute Myocardial Infarction

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Role of Adenosine in Acute Myocardial Infarction Presented by: Mervyn B. Forman, MD, PhD, FACC

  2. Potential Sequelae of Reperfusion on Ischemic Myocardium • Reperfusion Injury • Conversion of reversibly injured endothelial and myocardial cells to irreversibly injured cells • Myocardial Stunning • Prolonged left ventricular dysfunction of reversibly injured myocytes • Reperfusion Arrhythmias

  3. Myocardial Reperfusion Injury • Definition: Conversion of reversibly injured endothelial and myocardial cells to irreversibly injured cells during the peri-reperfusion period. Not synonymouswith entity of acceleration of necrosis of cells that are already irreversibly injured.

  4. Vascular Changes with Reperfusion

  5. Adenosine Receptors: SignalTransduction Mechanisms A3 A1 (Very high affinity) (Low affinity) Isoforms have distinct, but overlapping, cellular distribution and are widely expressed in most cells/tissues/organs of the body. Gi KATP PLA2 PLC Ca2+ AC Gs A2B A2A (Low affinity) (High affinity)

  6. Effects of Adenosine A1 A1

  7. Effects of Adenosine A2A/A2B A2A/A2B

  8. A3 Effects of Adenosine A3

  9. A2A/2B Angiogenesis Vasculogenesis ADENOSINE Mechanisms of Myocardial Reperfusion Injury and Effects of Adenosine Reperfusion TxA2, PAF, Ang II, NE, ET-1 Platelets Leukocytes Oxygen Calcium A3 A1 A2A A2A A2A Oxygen Free Radicals Cellular Calcium Overload MPO Proteases Platelet Aggregation Vasoconstriction Vascular Plugging No Reflow Cell Death

  10. 50% Control 44% 42% Adenosine 40.9% * p<0.001 40% **p=0.002 30% 18% 20% * 9.9% ** 4.6% 10% 0% AR/LV AN/AR AN/LV Infarct Size with Intracoronary Adenosine Olafsson et al. Circulation 1987; 76:1135-45

  11. 50 Control * 39.1 Adenosine 40 35.3 * p<.05 30.2 **p<.01 30 (%) ** 17.1 20 11 10 7 0 AR/LV AN/AR AN/LV Effect of IV Adenosine Pitarys et al. Circulation 1991; 83: 237-47

  12. Transverse Myocardial Slice in Adenosine and Control Animal

  13. Control Adenosine * p<.03 **p<.01 Control *p< .03 Adenosine **p < .01 * 25 20 ** 21 20 20 ** 17.3 ** ** 15 (%) 11 Ischemic Zone Radial 10 Shortening (%) 10 5.5 5 0 -2.6 -5 0 Base OCC Rep 3H Rep 72H  RS OCC vs 3H RS OCC vs 72H Regional Ventricular Function in Ischemic Zone Significant improvement noted at 3 and 72 hours after reperfusion. Pitarys et al. Circulation 1991; 83: 237-47

  14. 30 27 ADO ADO Saline Saline 25 * 19 *p< 0.05 *p= 0.0001 20 Number of Patients 15 100% * 7 10 80% * 5 64% 1 60% 0 TIMI 3 No-Reflow (%) 36% 40% 25 23 ADO 19% Saline * 20% 20 *p < 0.05 * 16 2% 15 13 0% Number of Patients Remodeling Recovery 10 * 5 5 5 * 0 0 Q wave MI Death MACE IC Adenosine with PCI in AMI Marzilli et al. Circulation 2000; 101:2154-2159

  15. 80 n=38 n=96 Adenosine Placebo n=101 n=39 n=58 60 n=62 p=0.014 p=0.085 % of Left Ventricle 45.5 p=0.96 40 20 19.5 15 13 11.5 11.5 0 Overall (33% reduction) Anterior (67% reduction) Nonanterior (0% reduction) Final Infarct Size (as a Percentage of the Left Ventricle) Median values shown above horizontal lines AMISTAD TRIAL. J AM Coll Cardiol 1999; 34: 1711-20

  16. 2118 Patients ASA Placebo Adenosine 50mcg/Kg/min X 3h Adenosine 70mcg/Kg/min X 3h Fibrinolysis or PTCA Infarct size (5 d) (243 patients) Follow-up for 6 months AMISTAD II • Anterior Wall MI (STE, LBBB) 6h • No contraindication for lysis • No hypotension • No bradycardia • No obstructive airway disease

  17. AMISTAD II – Non MACE Adverse Events

  18. Median LV Infarct Size (%) Median LV Infarct Size (%) p=0.028 p=0.078 40% 40% p=0.122 30% 30% 26% 26% 23% 17% 20% 20% 11% 10% 10% 0% 0% Placebo Pooled Adenosine 50 mcg 70mcg Placebo AMISTAD II Infarct Size 57% reduction in median infarct size with 70mcg/kg/min group relative to placebo

  19. Placebo 20% Pooled Adenosine 17.2% * p=0.01 15% **p=0.03 + 12.0% + p=0.02 11.2% 9.2% 10% ** 7.3% * 5.2% 5% 0% Death at 1 Death at 6 Composite month months 6 months AMISTAD II- Post Hoc Analysis Effect of early reperfusion treatment (3.1 hrs) on clinical outcomes

  20. 70 CONTROL ADENOSINE * P<0.03 (ADO vs. CONTROL P<0.01 (ADO vs. CONTROL) ** 40 AN/AR (%) 30 20 ** 10 * 40 MIN 180 MIN 120 MIN Effect of Adenosine with Varying Duration of Ischemia

  21. Complete Censored 1.00 0.95 0.90 Adenosine-anterior 0.85 0.80 Placebo-anterior 0.75 R.R. 0.64, 95% C.I. 0.37 – 1.11, p = 0.13 0.70 600 800 1000 1200 1400 0 200 400 Overall Survival Curves Cumulative Proportion Surviving Time (days) ATTACC Study. Eur J Clin Pharmacol 2003; 59:1-9

  22. Key Points • Adenosine shown consistently to reduce infarct size • 70mcg/kg/min infusion for 3 hours shows 57% relative reduction in infarct size • Strong trend toward less death and CHF • Significant reduction in death and composite endpoint at 6 months in Adenosine group treated early (~3.1 hrs) -post hoc analysis MI patients who undergo reperfusion therapy:

More Related