The rupture of an atherosclerotic plaque does not always result in complete occlusion of the epicardial coronary artery with subsequent impending acute myocardial infarction. In fact, plaque rupture with some persistent antegrade flow results in embolization of the atherosclerotic and thrombotic debris into the coronary microcirculation; coronary microembolization is a key event in acute coronary syndromes and a frequent complication of percutaneous coronary interventions.

We have developed a dog/pig model of coronary microembolization with intracoronary infusion of polystyrene microspheres (42 mm diameter). Upon acute coronary microembolization, coronary blood flow is immediately reduced but then exhibits reactive hyperemia whereas contractile function deteriorates progressively over several hours and then recovers slowly over about one week. The state of coronary microembolization is thus characterized by perfusion-contraction mismatch, as well as by patchy microinfarcts and an inflammatory response. The signal transduction of the observed profound contractile dysfunction involves nitric oxide, TNFa, sphingosine and oxidative modification of the cardiomyocyte contractile machinery. Cortison largely attenuates the contractile dysfunction, emphasizing its inflammatory nature. The upregulation of TNFa is an autocrine response of cardiomyocytes in the immediate vicinity of microinfarcts; TNFa not only causes contractile dysfunction but also induces delayed protection against myocardial infarction. In contrast, coronary microembolization does neither induce nor interfere with acute ischemic preconditioning.

In patients undergoing percutaneous coronary interventions, the plaque debris can be retrieved with protective occlusion/aspiration devices. Plaques with a necrotic core are particularly prone to coronary microembolization. The aspirate is characterized not only by particulate debris, but also by soluble vasoconstrictor (serotonin, TxA2) and inflammatory (TNFa) components. Microembolic signals can be obtained with intravascular ultrasound and the resulting microcirculatory damage be visualized by delayed contrast MRI. Microembolization in patients, as in the experiment, impairs coronary reserve. Statin pretreatment reduces coronary microembolization.

Supported by the German Research Foundation