Platelets and Vascular Occlusion

Coronary angiography has proved beyond doubt that complete coronary occlusion is the rule in the very early hours of infarction. The 60% to 80% rate of coronary recanalization after thrombolytic therapy has proved that thrombosis is a major component of the occlusion at the time when the procedure is performed a few hours after the onset of symptoms. However, the trigger for coronary thrombosis and the causes of failure of thrombolytic therapy are still a matter of speculation. The relatively rare occurrence of acute coronary occlusion in the life of an individual with even severe coronary disease can be explained on the basis of the necessity of either (1) extremely powerful isolated stimuli, which only occurs rarely, or (2) the casual simultaneous presence in one coronary arterial segment of multiple unfavorable events, such as plaque fissuring, enhanced reactivity of coronary smooth muscle to constrictor stimuli and displacement of the thrombotic-thrombolytic equilibrium toward thrombosis. Coronary artery constriction possibly caused by vasonconstrictor substances released by thrombus, represents the potential element of a vicious cycle causing persistent coronary occlusion and reocclusion when reflow occurs with thrombolysis. Circulation 73, No. 2, 233-239, 1986. THE NOTION of coronary artery occlusion is traditionally associated with that of myocardial infarction. However, total coronary occlusions in the absence of infarction are frequently observed both during angiographic and postmortem examination in patients without symptoms or signs of ischemic events. Coronary occlusions are most likely to cause myocardial necrosis when occurring suddenly in vessels that are not already critically obstructed and have no adequate or no functional distal collaterals. Conversely, when occlusions are not associated with detectable ischemic events they probably developed gradually in vessels with distal functioning collaterals.i The alternative view, that coronary occlusion may be a consequence rather than a cause of infarction,2 although attractively explaining some puzzling observations,3 lacks objective evidence. Thus it seems reasonable to assume that the development of infarction is usually determined by the balance between four factors: (1) the rate of progression of the occlusion, (2) its duration or intermittance, (3) the extent of collateral blood flow, and (4) the coronary and myocardial response to ischemia. We will consider only the mechanisms of acute From the Royal Postgraduate Medical School, Hammersmith Hospital, London. Supported by British heart Foundation and Medical Research Council programme grant PG979/1033. Address for correspondence: Attilio Maseri, M.D., Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London W12 OHS, England. Vol. 73, No. 2, February 1986 coronary occlusion, attempting to separate facts from extrapolations so that future lines of research can be defined from a more rational basis. Evidence for coronary occlusion in the early phases of infarction. The angiographic studies by De Wood et al.4 have definitively clarified the issue by showing beyond doubt that, in the first 4 hr of the onset of symptoms, the coronary artery supplying the infarcted area is indeed occluded in over 87% of patients and is patent, although severely narrowed, in the remaining 13%. These findings have been largely confirmed by subsequent reports on intracoronary thrombolysis. It is conceivable that in the few cases in which the artery was found to be patent, it may have been occluded previously, since occlusions do tend to recanalize spontaneously and patent vessels are found in 32% of patients within 12 hr4 and in about 50% at 2 to 3 weeks.5 Therefore, because enough evidence has now been gathered to establish that the coronary artery supplying the infarcted region in indeed totally occluded, at least in the early phases of infarction, it is appropriate to discuss the nature of the occlusion and its initiating mechanisms. Nature of the acute coronary occlusion. From a theoretical point of view, acute coronary occlusion may be caused by intravascular plugging by blood constituents, by some form of vasospasm (see below), by embolization, by intraplaque hemorrhage, or possibly more often by a variable combination of these factors. 233 by gest on O cber 9, 2017 http://ciajournals.org/ D ow nladed from