Abstract WP148: Magnetically Enhanced Diffusion (MED) Of Intravenous Thrombolytics Decreases Thrombus Leading To Accelerated Reperfusion

Abstract

Whether systemic fibrinolysis alone or, more recently, combined with thrombectomy are used to re-establish blood flow in cerebral arteries occluded with thrombus, a shower of fragments often plugs more distal arterial branches leading to continued infarction, resulting in some loss of brain function. We hypothesized that magnetite MicroBeads injected intra-arterially near a thrombus and exposed to a rotating magnetic field after IV administration of plasminogen activators (lytics) would accelerate fibrinolysis leading to decreased distal thrombus burden, increased blood flow, and less brain infarction and loss of function. Clots formed in vitro from recalcified citrated rabbit blood were weighed (ave = 100mg) and injected into both common carotid arteries with blood flow occluded at the level of C3/4 in anesthetized male and female rabbits. rtPA (Activase, 1mg/kg, Genentech) was infused IV over 1h or Tenecteplase (TNK, 0.3-0.9mg/kg, Genentech) was injected IV as a bolus. After 30 min, magnetite MicroBeads were injected (300ug) as a bolus every 5 min over 30min (6 doses, 1,800mg) through a 5F angiocatheter placed within 2-3cm of the clot in one carotid, while the other carotid received the lytic alone by diffusion. The clots were removed after 1h and reweighed. MED increased the rate of fibrinolysis of clots leading to &gt95% reduction in clot weight vs 83% with Activase alone (p&lt0.0001 for paired testing, n=8). Clot lysis was also increased with MED + TNK (p&lt0.05, n=6) compared to TNK alone. Thus significant acceleration of lysis and reduction in clot weight occurs after treatment with MicroBeads plus lytic compared to lytic alone. This approach may enhance reperfusion and decrease infarction during stroke treated by either lytic alone or lytic + thrombectomy leading to improved outcomes.