Corstiaan den Uil, M.D., Ph.D. Erasmus MC WES symposium Rotterdam 14 maart 2014
No ST elevation Stable angina
Unstable angina
NSTEMI
ST elevation STEMI
ACUTE CORONARY SYNDROMES
IschemiaRelated Injury
Reperfusion Injury
Infarct Size
Individual Factors
Distal Embolization
IschemiaRelated Injury
Reperfusion Injury
Infarct Size
Individual Factors
Distal Embolization
Pharmacological Facilitation of Coronary Intervention in ST-Segment Elevation Myocardial Infarction: Time Is of the Essence⁎ J Am Coll Cardiol Intv. 2010;3(12):1292-1294. doi:10.1016/j.jcin.2010.08.024
Decline in Deaths from Cardiovascular Disease in Relation to Scientific Advances.
IschemiaRelated Injury
Reperfusion Injury
Infarct Size
Individual Factors
Distal Embolization
1. Thrombus aspiratie
2. Clearway Catheter: Intracoronary Abciximab
Localized Drug Delivery via ClearWay for Pharmacological Thrombectomy and Prevention of Distal Embolization
3.
Typ hier uw tekst
The MGuard and MGuard Prime Embolic Protection Stent (EPS)
MGuard Prime L605 cobalt chromium 80 µm 1.0 – 1.2 mm 0.65 – 0.86 mm PET** 20 µm 150 - 180 µm
*InspireMD, Tel Aviv, Israel; **Polyethyleneterephthalate
Thrombus Entrapment by the MGuard in STEMI
Pre
Post aspiration Jain AK and Rothman MT. JACC 2011;58;e39
Residual thrombus
Thrombus Entrapment by the MGuard in STEMI
Mesh Post MGuard Jain AK and Rothman MT. JACC 2011;58;e39
Thrombus trapped behind mesh
4.
IschemiaRelated Injury
Reperfusion Injury
Infarct Size
Individual Factors
Distal Embolization
Standard treatment (314) IV insulin 48 hours, then 4 injections daily (306) Low-Risk & Not Previously on Insulin (N=272)
All Subjects (N=620)
0.7 0.6 0.5
0.7
Risk reduction (28%)
0.6
P=.011
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
0
0
0
1
2
3
Follow-Up (y)
4
5
Risk reduction (51%) P=.0004
0
1
2
3
4
5
Follow-Up (y)
MI = myocardial infarction; DIGAMI = Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction. (Short and long term effect of intensive insulin therapy) 44vs33 Malmberg K et al. BMJ. 1997;314:1512-1515.
IschemiaRelated Injury
Reperfusion Injury
Infarct Size
Individual Factors
Distal Embolization
Yellon DM, Hausenloy DJ. N Engl J Med 2007;357:1121-1135.
Reperfusion injury Infarction size
Reperfusion
Ischemia
Time
Role of the Mitochondrial Permeability Transition in Apoptosis and Necrosis Cytokines e.g. TNF, Fas
Removal of growth factors
Stresses e.g. reperfusion or toxins
Multiple and interacting signalling pathways Mitochondrial Permeability Transition
Activation of Caspase 8
?
t-Bid and Bax migrate to mitochondrial outer membrane
Activation of caspase 3
Induction of apoptotic cascade
APOPTOSIS
Activation of caspase 9
Swelling and outer membrane rupture
Transient opening
-
bcl-2
- ? bcl-2
Release of cytochrome c, Smac/Diablo and AIF
Apoptosis requires ATP levels to be maintained, whereas in necrosis ATP levels fall. Transient MPT opening allows some swelling of mitochondria and cytochrome c release, but on resealing ATP levels can be restored allowing apoptosis to occur.
Prolonged opening
NECROSIS
1. From: Acute Myocardial Infarction With Hyperoxemic Therapy (AMIHOT): A Prospective, Randomized Trial of Intracoronary Hyperoxemic Reperfusion After Percutaneous Coronary Intervention J Am Coll Cardiol. 2007;50(5):397-405. doi:10.1016/j.jacc.2007.01.099
Body Core Temperature (º C) * Am J Physiol Heart Circ. Physiol 1996; 270: H1189-99
40
3. Ischemic Preconditioning (IPC) 1986 Murry et al. In situ dog hearts
5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’
40’ 4d
I R I R I R I R
Ischaemia R
75% Infarct size reduction However, clinical application restricted
Murry et al. Circulation 1986 acute coronary syndromes
30
18-03-2013
Ischemic Postconditioning (IPOC) 2003 Zhao et al. Inhibition of myocardial injury by IPOC as potent as IPC Easy clinical application In situ dog hearts Control 60 min I
