Preclinical Investigations for Thrombectomy Devices—Does it Translate to Humans?

Abstract

In the United States, 4 devices have received Food and Drug Administration clearance for intra-arterial mechanical removal of the embolus in a large vessel occlusion causing acute ischemic stroke (AIS). A number of other devices with similar indication are either beginning trials in the United States or are available for clinical use in the European Union. The goal of preclinical modeling for the intra-arterial treatment of AIS is to evaluate the safety and the efficacy of these devices quantitatively to predict how they will perform in patients, identify effective techniques for their use, or to optimize the design before introducing them into clinical trials. Safety studies should ascertain the potential for vascular trauma, propensity to generate distal emboli, and effect on the blood brain barrier, particularly in the case where the device is used to deliver energy for clot disruption. Efficacy metrics include the ability to restore flow through the occluded vessel (recanalization), the amount of flow restored to the distal territory (reperfusion), and the time needed to remove the embolus. Large animal models of stroke amenable to the study of endovascular mechanical thrombectomy are challenging because of the anatomy of the cerebrovasculature in commonly used laboratory animals.1 To date, most preclinical modeling uses large vessel occlusion in the extracranial circulation of the pig2–5 or dog,4,6 wherein the selected vessel is embolized with an autologous clot of varying composition. Notably, these are not models of AIS and, therefore, the traditional end points of infarct volume and neurological outcome are not applicable. Therefore, the end points of these studies are typically angiographic evidence of recanalization and pursuant damage to the vessel in which the device was operated. Importantly, the architecture of the extracranial vasculature with substantial perivascular support, external elastic lamina, and robust tunica media is …