Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation.

Abstract

Endovascular treatment of ischemic stroke usually involves recombinant tissue-type plasminogen activator (rtPA)-mediated thrombolysis in anesthetized patients. Paradoxically, differential influences of anesthetic agents on thrombolysis outcome remain unknown. In situ thrombotic stroke was induced in mice by local injection of thrombin. Four hours after the ischemic onset, mice underwent rtPA-mediated thrombolysis either awake or subjected to different anesthetic regimens (propofol, isoflurane/N2O, ketamine). Infarct volume and arterial recanalization were assessed by MRI at 24 hours. Whatever the anesthetic regimen, infarct volumes measured at 24 hours were not affected. However, in contrast with other anesthetic agents tested, ketamine dramatically reduced infarct volume when combined with rtPA. Altogether these data suggest that ketamine significantly improves the benefit of rtPA-induced thrombolysis after stroke.