Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis

Yang, Zijiang; von Ballmoos, Moritz Wyler; Diehm, Nicolas; Baumgartner, Iris; Kalka, Christoph; Di Santo, Stefano (2009). Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis. Vascular pharmacology, 51(4), pp. 268-74. New York, N.Y.: Elsevier 10.1016/j.vph.2009.07.001

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A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athymic rnu-rats by surgical excision of the femoral vessels. Blood flow of the limb was monitored for 60 days by laser Doppler imaging. Following a short postoperative period of substantially depressed perfusion, the animals showed a status of moderate hind limb ischemia from day 14 onwards. Thereafter, the perfusion remained at a constant level (55.5% of normal value) until the end of the observation period. Histopathological assessment of the ischemic musculature on postoperative days 28 and 60 showed essentially no inflammatory cell infiltrate or fibrosis. However, the mitochondrial activity and capillary-to-fiber ratio of the muscular tissue was reduced to 52.7% of normal, presenting with a significant weakness of the ischemic limb evidenced by a progressive decline in performance. Intramuscular injection of culture-expanded human endothelial progenitor cells (EPC) resulted in a significant increase in blood flow (82.0+/-3.5% of normal), capillary density (1.60+/-0.08/muscle fiber) and smooth muscle covered arterioles (8.0+/-0.6/high power field) in the ischemic hind limb as compared to controls (55.0+/-3.1%; 0.99+/-0.03; 5.0+/-0.2). In conclusion, chronic, moderate hind limb ischemia with consistently reduced perfusion levels persisting over a prolonged period can be established reliably in rnu athymic nude rats and is responsive to pro-angiogenic treatments such as EPC transplantation. This study provides a detailed protocol of a highly reproducible reference model to test novel therapeutic options for limb ischemia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology

UniBE Contributor:

Yang, Zijiang; Diehm, Nicolas Alexander; Baumgartner, Iris; Kalka, Christoph and Di Santo, Stefano

ISSN:

1537-1891

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.1016/j.vph.2009.07.001

PubMed ID:

19619670

Web of Science ID:

000271283700007

URI:

https://boris.unibe.ch/id/eprint/32066 (FactScience: 196934)

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