Abstract W MP34: Magnetically-Enhanced Diffusion (MED) of Intravenous tPA for Acute Ischemic Stroke: Preclinical Data
Background: Diffusion of drug to the clot in a no flow environment may be a major factor in the relative ineffectiveness of iv-tPA. The MED system uses an external magnet and magnetic particles (MP) to improve IV-tPA diffusion to clots and to mix tPA at the clot surface. Methods: Diffusion experiments were conducted in a femoral artery ligation model using Evan’s Blue dye as surrogate to tPA. Clot surface interaction experiments were conducted in a jugular vein rabbit model using thrombin-induced occlusions. tPA was locally delivered. Time to recanalization was measured out to 3hrs for 312.5U to 5000U of tPA in ~500uL of blood (0.6U/uL and 9.9U/uL, respectively), with and without MP.
Results: Femoral dye studies showed a >5X faster diffusion using the MED system in the femoral artery (Figure 1). Jugular lysis studies showed greater variability in the tPA-alone arm, which possessed several failures to recanalize. No recanalization occurred in <30min for tPA doses <2500U. <25% of the 625U doses restored flow in <1hr. Use of the MED system substantially improved tPA lysis reliability (all recanalization <140min for all doses). 67% of the 625U doses restored flow <1hr. Compared to successful tPA recanalization alone, scatter was significantly smaller and time-to-recanalization 2.5X faster (Figure 2).
Conclusion: This study demonstrates the ability of the MED system to accelerate both tPA transport to a clot and clot lysis. This observation supports efficacy signals seen in the human feasibility trial. These results may provide a new understanding of the variability historically seen in thrombolytic efficacy, which may be related to inefficient thrombolytic contact with the thrombus.
Author Disclosures: C. Derdeyn: Ownership Interest; Modest; Pulse Therapeutics. Consultant/Advisory Board; Modest; Microvention, Penumbra, Silk Road, Pulse Therapeutics. C. Bladin: None. C. Levi: None. M. Parsons: None. B. Campbell: None. P. Panagos: Speakers' Bureau; Modest; Genentech. Consultant/Advisory Board; Modest; Pulse Therapeutics. F. Creighton: Employment; Significant; Pulse Therapeutics. Ownership Interest; Significant; Pulse Therapeutics.
- © 2015 by American Heart Association, Inc.