The potential of monoclonal antibodies to reduce reperfusion injury in myocardial infarction

Reperfusion injury is mediated, in part, by the accumulation of platelets a nd leucocytes in the microvasculature after reflow. These components of the blood pool form aggregates that can obstruct flow in small vessels. In add ition, mediators released from leucocytes and platelets further damage the reperfused myocardium. A strategy to limit reperfusion injury exploits the important role of membrane-bound adhesion molecules that attach platelets a nd leucocytes to themselves and to the vascular endothelium. Monoclonal ant ibodies against specific adhesion receptors effectively eliminate the funct ion of the receptor. The most widely investigated receptors are P-selectin, present on platelets and the endothelium, CD11/CD18, present on leucocytes , and the fibrinogen receptor on platelets. Numerous animal studies have st rongly supported the use of these monoclonal antibodies to block adhesion r eceptors as adjunctive reperfusion therapy. However, recent human trials ha ve yielded disappointing results.