Effects of hypercholesterolemia on healing of vascular grafts

Howard P. Greisler, John J. Klosak, Eric D. Endean, John F. Mcgurrin, Jacqueline D. Garfield, Dae Un Kim

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Small-diameter vascular grafts woven from bioresorbable lactide/glycolide copolymers have been successfully interposed into aortas of normal NZW rabbits. The current study examines the histologic and functional reactions to these bioresorbable grafts in severely hypercholesterolemic rabbits, a standard animal model of atherosclerosis. Sixty rabbits were placed on a 2% cholesterol, 6% peanut oil atherogenic diet. Baseline serum cholesterols and triglycerides were measured and repeated at operation 3 months later. Woven polyglactin 910 (PG910) grafts were interposed into infrarenal aortas. Fifty-two rabbits died on the diet or within 3 days of surgery and eight survived operation (normal NZW rabbit operative mortality is < 10% Cholesterol levels rose from 63 to 1989, p < 001. Of the eight survivors, five died after 3 weeks, and one died after 21/2 months. Two were sacrificed at 2 and 4 months. Four aortic disruptions with retroperitoneal hematomas, one pseudoaneurysm, and one diffuse aneurysm were observed, greater than in normal rabbits, p < 001. Inspection revealed severe atherosclerosis. Histologically, 3-week explants showed only small areas of neointima with myofibroblasts and endothelial cells; the outer capsules were infiltrated by lipid-laden macrophages. Graft material in 2-to 4-month explants was replaced by tissue with histologic atherosclerosis. More severe atherosclerosis was observed in native aortas at the perianastomotic areas than the more distant aortic segments. Abundant intracellular lipid was seen also in splenic histiocytes and hepatic cells with evidence of micronodular cirrhosis. Macrophages phagocytizing bioresorbable prostheses may release growth factors mediating the formation of a cellular tissue conduit. Severe hypercholesterolemia may alter monokine release from macrophages resulting in a weakened prosthesis/tissue complex.

Original languageEnglish
Pages (from-to)299-312
Number of pages14
JournalJournal of Investigative Surgery
Issue number3
StatePublished - 1991

Bibliographical note

Funding Information:
The authors acknowledge the assistance of Sheryl L. Andrus in the preparation of electron micrograph materials and of Dolores Breen in the preparation of the photomicrographs. This work was supported, in part, by a grant from the National Institutes of Health, number R01 HL41272.


  • Atherosclerosis
  • Bioresorbable materials
  • Cholesterol
  • Macrophage
  • Rabbit
  • Vascular grafts

ASJC Scopus subject areas

  • Surgery


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