Asymmetric Dimethylarginine in Response to Recombinant Tissue-Type Plasminogen Activator and Erythropoietin in Acute Stroke

Background and Purpose—In the German Multicenter Erythropoietin (EPO) Stroke Trial, patients not receiving thrombolysis most likely benefited from EPO on clinical recovery, whereas a combination of rtPA and EPO was associated with increased mortality. We investigated whether the combination of rtPA and EPO increased release of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA), and thereby potentially deteriorated ischemic stroke outcome, as suggested from experimental data.

Methods—ADMA was determined in serum samples from 90 patients of the German Multicenter EPO Stroke Trial taken at days 1 (within 6 hours after symptom onset), 2, 3, 4, and 7 after stroke using high-performance liquid chromatography–tandem mass spectrometry. ADMA was analyzed for the different treatment groups (EPO, n=25; placebo, n=30; rtPA+placebo, n=18; EPO+rtPA, n=17). Clinical outcome was expressed as difference between National Institutes of Health Stroke Scale at baseline and 90 days. Read More