Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part I: kidney

Using a pig model: (1) to evaluate the vascular distribution pattern, including the homogeneity and completeness of the intra-arterial microsphere distribution, of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in acute whole-kidney embolization; (2) to evaluate the durability and biocompatibility of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in chronic partial kidney embolization. Twenty-two animals were divided into four groups: group 1 (n = 4) underwent total arterial renal occlusion with immediate euthanasia. Groups 2-4 had chronic superselective and partial renal embolization with increasing follow-up times: group 2 (n = 2), 1 week; group 3 (n = 7), 4 weeks; and group 4 (n = 9), 14 weeks. Key endpoints in group 1 were homogeneity and completeness of acute embolizations. In groups 2-4 the key endpoints were durability of embolization and particle-related inflammation in chronic partial embolizations as assessed by quantitative angiography or histomorphometry. A numerical angiographic occlusion score (0.0 to 4.0, where 3.0 is optimal) was developed to assess and quantify the angiographic durability of superselective embolizations (groups 2-4). In group 1, a relatively homogeneous distribution of the particles from segmental arteries to the precapillary level was shown by histomorphometry. Some particles reached the glomerular vas afferens (10 microm diameter). In groups 2-4, a mild recanalization appeared during follow-up. The immediate average postembolization occlusion score of 3.18 +/- 0.73 was reduced to 1.44 +/- 0.73 (statistically significant). Microscopy revealed subtotal necrosis but no foreign body granuloma formation. The intra-arterial appearance of giant cells closely attaching to the surface of the embolic spheres inside the vessel lumen was noted. Vessel walls showed major ischemic reactions. Microspheres 40-120 microm in diameter might achieve total occlusion of the arterial kidney vasculature when injected centrally as a result of their fairly homogeneous distribution. Segmental renal infarction occurs after chronic partial embolization despite recanalizations during follow-up. Only mild specific intra-arterial foreign body reactions were found.