Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection

Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hem orrhage (ICB) may reduce mass effect and edema development and improve outc ome. To test this hypothesis, the authors induced lobar hematomas in pigs. Methods. The authors infused 2.5 mi of blood into the frontal cerebral whit e matter in pigs weighing 8 to 10 kg. In the treatment group, clots were ly sed with tissue plasminogen activator ([tPA], 0.3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post -ICH and hematomal and perihematomal edema volumes were determined on coron al sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 +/- 1.3 to 2.8 +/- 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 +/- 0.10 compared with 1.26 +/- 0.13 cm(3), p < 0.005) and perihematomal edema volumes (0.28 +/- 0.05 compared with 1. 46 +/- 0.24 cm(3), p < 0.005), compared with unevacuated control lesions. F urthermore, no Evans blue dye staining of perihematomal edematous white mat ter was present in brains in which the hematomas had been evacuated, compar ed with untreated controls. Conclusions. Hematomas were quickly and easily aspirated after treatment wi th tPA, resulting in significant reductions in mass effect. Hematoma aspira tion after fibrinolysis with tPA enabled removal of the bulk of the hematom a (> 70%), markedly reduced perihematomal edema, and prevented the developm ent of vasogenic edema. These findings in a large-animal model of ICH provi de support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.