Plasma 3-nitrotyrosine estimates the reperfusion-induced cerebrovascular stress, whereas matrix metalloproteinases mainly reflect plasma activity: a study in patients treated with thrombolysis or endovascular recanalization

Cerebral reperfusion injury may account for complications of thrombolysis and endovascular recanalization. Experimental studies have shown that brain matrix metalloproteinase (MMP) activity increases during reperfusion and is correlated with oxidative/nitrative stress. Increased plasma MMP levels have been reported in stroke, but no information is available for reperfusion-induced plasma MMP and 3-nitrotyrosine (3-NT, a marker of oxidative/nitrative stress) changes immediately after recanalization. We obtained plasma from 29 patients undergoing endovascular recanalization, 12 patients treated with thrombolysis, and six control patients having diagnostic angiogram before and 1,3, and 24 h after treatment to investigate the effect of cerebral reperfusion on plasma MMP gelatinolytic activity and 3-NT level. Hypoperfusion was shown distal to the stenotic artery in endovascular treatment patients. Presence of an occluded artery and recanalization was documented in thrombolysis patients. A significant increase was detected in plasma 3-NT levels 3 and 24 h after stenting/angioplasty. Plasma MMP-9 gelatinolytic activity rose more than 50% of the pre-treatment level in 12 of 29 patients. However, this was not statistically significant and not correlated with any of the clinical or radiological correlates of reperfusion injury (e.g., hyperperfusion and hemorrhage). After thrombolysis, a significant increase in plasma MMP-9 gelatinolytic activity at 3 and 24 h and the cleaved form of MMP-9 were detected. 3-NT levels increased by 44% and 62% at 3 and 24 h, which did not achieve statistical significance, but was highly correlated with admission NIH Stroke Scale (r = 0.930 p < 0.001). No change was detected in MMP-2 in all groups. In conclusion, these data suggest that the increased plasma MMP-9 levels is not a direct measure of MMP-9 activity in the reperfused brain but rather a consequence of tissue plasminogen activator infusion, whereas plasma 3-NT levels appear to originate from the reperfused brain vasculature. The changes in 3-NT levels may therefore be useful to monitor oxygen/nitrogen radical formation during reperfusion with serial measurements.