Copyright © 2005, European Society of Cardiology
Simultaneous integrin 
vβ3 and glycoprotein IIb/IIIa inhibition causes reduction in infarct size in a model of acute coronary thrombosis and primary angioplasty
Cardiovascular Division, Box 800158, Medical Center, University of Virginia, Charlottesville, VA 22908-0158, United States
* Corresponding author. Tel.: +1 434 924 5928; fax: +1 434 982-3183. Email address: sk{at}virginia.edu
Objective: We tested the hypothesis that simultaneous inhibition of the endothelial integrin 
vβ3 and the platelet glycoprotein IIb/IIIa receptor will substantially reduce infarct size in a model of acute coronary thrombosis and primary angioplasty.
Methods: Dogs were subjected to thrombus formation in the left anterior descending coronary artery followed by primary angioplasty. Prior to angioplasty, they were randomized into 3 treatment groups. Group 1 (n=7) received saline; Group 2 (n=9) received MK-383 that inhibits only IIb/IIIa; and Group 3 (n=9) received CP-4715, that inhibits both IIb/IIIa and vβ3.
Results: There was a 59% reduction in infarct size in dogs receiving CP-4715 compared to controls (p=0.002) and a 37% reduction compared to the dogs receiving MK-383 (p=0.04). Myocardium microthrombi were seen to be reduced similarly with both drugs on post-mortem 99mTc-DMP444 autoradiography that reflects in vivo IIb/IIIa receptor activity. In vivo imaging using echistatin-conjugated and leukocyte-targeted microbubbles revealed significant vβ3 inhibition and reduction in active leukocyte recruitment only in Group 3 dogs. Myocardial blood flow and regional function after reperfusion were also significantly better in this group.
Conclusion: Simultaneous inhibition of IIb/IIIa and vβ3 causes a marked reduction in infarct size in a model of acute coronary thrombosis and primary PTCA that is associated with reduced myocardial microthrombi and inflammation, as well as improved myocardial blood flow and regional function. These results may have important implications in the treatment of acute coronary syndromes.
KEYWORDS Infarction; Echocardiography; Microcirculation; Reperfusion; Inflammation
Presented in part at the 52nd Annual Scientific Session of the American College of Cardiology, April 2003, in Chicago
Time for primary review 15 days
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