Korean J Radiol.  2007 Oct;8(5):418-428. 10.3348/kjr.2007.8.5.418.

Degradable Gelatin Microspheres as an Embolic Agent: an Experimental Study in a Rabbit Renal Model

Affiliations
  • 1Department of Radiology, Shiga University of Medical Science, Shiga, Japan. junryuhei@belle.shiga-med.ac.jp
  • 2Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

Abstract


OBJECTIVE
To investigate the basic characteristics of degradable gelatin microspheres (GMSs), including their embolic behavior and degradation periods when they are used as embolic materials in the renal arteries of rabbit models. MATERIALS AND METHODS: Based on the GMS particle size, 24 kidneys were divided into 3 groups of eight kidneys, and each group was embolized with a different GMS particle size (group 1: 35-100 micrometer, group 2: 100-200 micrometer, and group 3: 200-300 micrometer). From each group, two rabbits were sacrificed immediately after embolization (day 0), and a pair of rabbits from each group underwent an angiogram and were sacrificed on days 3, 7, and 14, respectively, after embolization. The level of arterial occlusion, the pathological changes in the renal parenchyma, and the degradation of the GMSs were evaluated angiographically and histologically. RESULTS: A follow-up angiogram on days 0, 3, 7, and 14 revealed the presence of wedge-shaped poorly-enhanced areas in the parenchymal phase as seen in all groups. The size of these areas tended to increase with the particle diameter, and persisted up to day 14. On days 3, 7, and 14, parenchymal infarctions were observed histologically in all cases, and this observation corresponded with the parenchyma being supplied by the embolized arteries. GMSs of group 1 mainly reached the interlobular arteries, while those of group 3 mainly reached the interlobar arteries. In all but two cases, the GMSs were identified histologically even on day 14, and sequential degradation was histologically identified in all GMS groups. CONCLUSION: GMSs can be used as degradable embolic materials which can control the level of embolization.

Keyword

Angiography; Microspheres; Embolism, experimental

MeSH Terms

Animals
Biocompatible Materials
Disease Models, Animal
Embolization, Therapeutic/*methods
Female
Follow-Up Studies
*Gelatin
Kidney/blood supply
*Microspheres
Particle Size
Rabbits
Renal Artery/drug effects/pathology/radiography
Renal Artery Obstruction/*chemically induced
Severity of Illness Index
Time Factors

Figure

  • Fig. 1 Microscopic appearance of gelatin microspheres (original magnification, ×100). Gelatin microspheres are spherical in shape when dispersed in double-distilled water.

  • Fig. 2 Comparison of the sizes of the poorly-enhanced areas in the angiogram of the parenchymal phase of the left renal artery after embolization using different-sized gelatin microspheres. (A) group 1: 35-100 µm; (B) group 2: 100-200 µm; and (C) group 3: 200-300 µm. The diameter of the poorly-enhanced areas was classified as large (greater than 7 mm: arrowhead) or small (less than 7 mm: arrow). In group 1 (A), the poorly-enhanced areas were small. Group 2 (B) showed both small and large poorly-enhanced areas, and group 3 (C) showed only large poorly-enhanced areas. Thus, the poorly-enhanced areas tended to increase with the diameter of the gelatin microspheres.

  • Fig. 3 Photomicrographic appearance of a resected kidney of group 1 (A) and group 3 (B) immediately after the embolic procedure. It was observed that the gelatin microspheres in group 1 frequently reached the interlobular arteries (arrow in A), while those of group 3 reached the interlobar arteries (arrow in B). (Hematoxylin & Eosin staining; original magnification, ×40)

  • Fig. 4 Photomicrographic appearance of the secondary changes in the vessel walls of group 1. A. Severe infiltration of leukocytes (arrows) that surrounded the gelatin microspheres was observed in the arcuate artery on day 3. Infarction of the renal parenchyma around this artery was demonstrated. B. Fibrosis (arrowheads) was observed in the wall of the interlobar artery around the gelatin microspheres on day 14; a decrease in the number of leukocytes was also observed (arrow). These reactions were similar to those caused by Gelfoam. (Hematoxylin & Eosin staining; original magnification, ×100)

  • Fig. 5 Sequential left renal angiograms showing the reperfusion of the interlobar arteries. (A) Angiogram immediately after the embolization; (B) angiogram on day 7; and (C) angiogram on day 14. A. The angiogram conducted immediately after embolization showed diffused poorly-enhanced areas of the renal parenchyma in group 1. B. The angiogram on day 7 showed that the parenchymal enhancement was restored, while the interlobar arteries were still poorly visualized. Small poorly-enhanced areas (arrows) were also found in the subcortical area. C. Angiogram on day 14 showed the recanalization of the interlobar arteries (arrowheads) with few remaining small poorly-enhanced areas (arrows). (case number: No. 7)

  • Fig. 6 Photomicrographic appearance of a resected kidney of group 1 on day 3 (A), day 7 (B), and day 14 (C). (Hematoxylin & Eosin stain; original magnification, ×100) A. Gelatin microspheres were completely solid and spherical, and degradation was not observed (arrow). B. Gelatin microspheres were spherical; however, some cleft-like cavities were found in the Gelalin micorphere particle (arrow). C. Gelatin microspheres were small and irregular in shape (arrow).


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