Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft

• Published in: Journal of vascular surgery Vol. 49; no. 5; pp. 1272 - 1281
• Main Authors: Kodama, Akio, MD, Komori, Kimihiro, MD, PhD, Hattori, Keisuke, MD, PhD, Yamanouchi, Dai, MD, PhD, Kajikuri, Junko, PhD, Itoh, Takeo, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.2009; Elsevier
• Subjects: Acetylcholine - pharmacology; Administration, Oral; Animals; Biological and medical sciences; Carotid Arteries - drug effects; Carotid Arteries - metabolism; Carotid Arteries - pathology; Carotid Arteries - physiopathology; Carotid Arteries - surgery; Cell Proliferation - drug effects; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Endothelium, Vascular - surgery; Enzyme Inhibitors - pharmacology; Hyperplasia; Jugular Veins - transplantation; Male; Medical sciences; Models, Animal; Neurosurgery; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - metabolism; Nitroarginine - pharmacology; Rabbits; Receptor, Serotonin, 5-HT2A - metabolism; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - pharmacology; Skull, brain, vascular surgery; Succinates - administration & dosage; Succinates - pharmacology; Superoxides - metabolism; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tunica Intima - drug effects; Tunica Intima - metabolism; Tunica Intima - pathology; Tunica Intima - surgery; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vertebrata; Mammalia; Animal; Surgery; Hyperplasia; Rabbit; Cardiovascular disease; Lagomorpha; Sarpogrelate
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2008.11.071

Objectives The selective 5-HT 2A receptor antagonist sarpogrelate has been clinically used for treatment in atherosclerotic diseases. However, it remains unknown whether administration of sarpogrelate inhibits intimal hyperplasia seen in autologous vein grafts. Therefore, we sought to clarify this question using an experimental rabbit vein graft model. Methods Male rabbits were divided into two groups: a control group and a sarpogrelate-treated group. The jugular vein was interposed in the carotid artery in reversed fashion for 4 weeks and intimal hyperplasia of the grafted vein was measured (n = 8, in each group). Acetylcholine (ACh)-induced endothelium-dependent relaxation was tested by precontraction with prostaglandin F 2α (PGF 2α , 5 μM) (n = 5, in each). endothelial nitric oxide synthase (eNOS) protein expression and superoxide production of these veins were also assessed. Results The suppression of intimal hyperplasia was significantly greater in the sarpogrelate-treated group than in the control group. ACh induced an endothelium-dependent relaxation in the sarpogrelate-treated group (but not in the control group). In endothelium-intact strips from the sarpogrelate-treated group, the nitric oxide (NO) synthase inhibitor nitroarginine enhanced the PGF 2α -induced contraction and blocked the ACh-induced relaxation. Immunoreactive eNOS protein expression was similar between the two groups but superoxide production (estimated from ethidium fluorescence) in endothelial cells was significantly smaller in the sarpogrelate-treated group. Conclusion The present results indicate that in vivo blockade of 5-HT 2A receptors leads to an inhibition of intimal hyperplasia in rabbit vein graft. It is suggested that an increased function of endothelium-derived NO through a reduction in endothelial superoxide production may be a possible underlying mechanism for this. These novel findings support the clinical usefulness of sarpogrelate for preventing intimal hyperplasia in vein graft after bypass grafting.