gms | German Medical Science

Objective: Hematoma puncture and clot lysis emerged as an alternative therapy for intracerebral hemorrhages (ICH). Recently, an international multicenter study (MISTIE trial) has been initated. However, we have shown in an animal study that recombinant tissue plasminogen activator (rtPA) to lyse ICHs is associated with delayed edema possibly counteracting the beneficial effects of hematoma volume reduction. We hypothesized that immediate reversal of rtPA activity after clot lysis and evacuation would diminish such edema. To test this hypothesis we administered plasminogen activator inhibitor one (PAI-1) following rtPA lysis of experimentally induced ICH.

Methods: Following placement of a right frontal/head of caudate intracerebral hematoma, pigs received either no further treatment (n=5), lysis with rtPA (n=7), or lysis with rtPA followed by administration of PAI-1 (n=6). Hematoma and edema volumes were assessed with magnetic resonance imaging on days 0, 4 and 10 and by histopathology on day 10.

Results: RtPA significantly contributed to delayed edema after experimentally induced hemorrhage (day 10 edema in no treatment group= 2 cc ± 1; tPA group= 12 cc ± 2). Administration of PAI-1 did not affect edema on day 4, but did diminish edema on day 10 (day 10 edema in tPA+PAI1 group= 6 cc ± 2). Cerebral water content as assessed by activated diffusion coefficient and T2 relaxation time increases in the tPA (mean 135 s) and tPA plus PAI groups (mean 180 s) at day 4 and then decreases more rapidly in the latter group at day 10 (tPA=110 s, tPA+PAI1=100s).

Conclusions: Delayed cerebral edema after rtPA lysis of experimental intracerebral hemorrhage is attenuated by administration of PAI-1. The combination of rtPA-clot lysis with PAI-1 has the potential to further improve the effect of the minimally invasive lytic therapy of intracerebral bleedings in the clinical setting.