American Society of Hirudotherapy

Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries

Research article published in Radiology (2001)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Clinical LiteratureDrug DevelopmentKalinowski M · Radiology, 2001

Abstract

PURPOSE: To determine if local application of L-arginine, r-hirudin, or molsidomine significantly reduces restenosis after balloon angioplasty in stenotic rabbit iliac arteries. MATERIALS AND METHODS: Thirty-one male cholesterol-fed New Zealand white rabbits underwent balloon dilation of both common iliac arteries to induce arterial stenosis. Four weeks later, one stenotic iliac artery was simultaneously dilated and received local application of L-arginine (210 mg/mL, n = 7), r-hirudin (0.5 mg/mL, n = 8), or molsidomine (0.2 mg/mL, n = 8) with a channeled balloon catheter. On the contralateral side, 0.9% saline was injected as a control. In eight sham animals, saline was applied to one iliac artery and balloon dilation to only the contralateral artery. Six weeks after local treatment, vessels were harvested, and computerized morphometric and immunohistologic analyses were performed. RESULTS: Application of drugs resulted in a significant reduction of neointimal area as follows: 53% with L-arginine (1.01 mm(2) vs. 2.17 mm(2), P <.05), 43% with molsidomine (1.04 mm(2) vs. 1.89 mm(2), P <.05), and 20% with r-hirudin (1.79 mm(2) vs. 2.24 mm(2), P <.05). Infusion of saline led to a significant increase (50%, 1.21 mm(2) vs. 1.93 mm(2), P <.05) in neointimal area compared with balloon dilation alone. Immunohistologic findings showed a significant reduction of macrophages (5.0% vs. 10.2%, P <.05) and proliferating cells (6.2% vs. 10.6%, P <.05) in the neointima after local application of L-arginine. CONCLUSION: Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arterial trauma, resulting in additional neointimal proliferation.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeComparative StudyJournal Article
Indexed MeSH termsAdministration, TopicalAngioplasty, BalloonAnimalsAntithrombinsArginineConstriction, PathologicHirudin TherapyHirudinsIliac ArteryMaleMolsidomineNitric Oxide DonorsRabbitsRecurrenceVasodilator Agents

Summary

In cholesterol-fed rabbits, local delivery via channeled balloon of L-arginine, molsidomine or r-hirudin after iliac angioplasty reduced neointimal area by 53%, 43% and 20% respectively, though the authors conclude the reduction was significant only for L-arginine and molsidomine.

Why This Matters for Hirudotherapy

This study examined whether local application of L-arginine, r-hirudin, or molsidomine via channeled balloon catheter could reduce restenosis after balloon angioplasty in stenotic iliac arteries of cholesterol-fed New Zealand white rabbits. The abstract reports that neointimal area reduction was significant for L-arginine (53%) and molsidomine (43%) but explicitly states in its conclusion that reduction was NOT significant for r-hirudin. The abstract refers only to 'r-hirudin' without mentioning leeches, leech origin, or hirudotherapy. Recombinant hirudin is produced in microorganisms from the gene of hirudin, the anticoagulant of the medicinal leech (Märki et al., 1991); this paper studies the drug, not leech therapy.

Citation

Reference (Vancouver style)

Kalinowski M, Alfke H, Bergen S, Klose KJ, Barry JJ, Wagner HJ. Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries. Radiology. 2001;219(3):716-723. doi:10.1148/radiology.219.3.r01jn27716. PMID: 11376260

Bibliographic details (authors, volume, pages, DOI) are taken from the PubMed record.

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.