Thrombolytic therapy in experimental embolic stroke.

The effect of thrombolytic therapy is well-documented in acute myocardial infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated in small series of patients. The point of thrombolytic therapy is to avoid or reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of reperfusion needs further investigation and documentation. This review describes studies of thrombolysis in embolic stroke using animals embolized by intracarotid injections of blood clots. Vascular occlusion was demonstrated by angiography and measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue-type plasminogen activator was initiated after varying periods of time. Reperfusion, cellular function, and brain damage were examined by angiography and by clinical and pathoanatomical examination. Based mainly on results from our own investigations, the following theses concerning ischemic stroke were made: (a) Cerebral infarction caused by arterial occlusion is due to delayed, incomplete, or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor importance. (b) Early thrombolytic therapy in animal models increases the degree of reperfusion and reduces brain damage, clinical deficits, and mortality. (c) Early arterial reperfusion reduces cerebral infarction and related edema. With early reperfusion, the extent of brain damage correlates to the length of the delay from onset of ischemia. (d) Cerebral stunning is caused by arterial occlusion followed by very early spontaneous or induced reperfusion, as neurons temporarily lose their functional capabilities without dying. (e) Multiple embolic microclots in experimental stroke result in more brain damage than a single macroclot, and with clots the extent of brain damage is dependent on the structural composition and volume of emboli. (f) The ability to recanalization in experimental embolic stroke is related to the amount of red cells in the emboli and inversely related to the volume of emboli and to the fibrin content and density of the clots. (g) Infarct-limiting effects in experimental stroke can be obtained by ischemic neuroprotectants or by hypothermia, either alone or with thrombolytic therapy, which then reduces brain damage further.