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This Article Full Text Full Text (PDF) Buy All Versions of this Article: 296/6/H1940    most recent 01177.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Droogmans, S. Articles by Van Camp, G. Search for Related Content PubMed PubMed Citation Articles by Droogmans, S. Articles by Van Camp, G.

Cyproheptadine prevents pergolide-induced valvulopathy in rats: an echocardiographic and histopathological study

Departments of ¹Cardiology, ²Nuclear Medicine, and ³Pathology, Universitair Ziekenhuis Brussel, and ⁴In Vivo Cellular and Molecular Imaging, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium

Submitted 11 November 2008 ; accepted in final form 2 April 2009

Serotonergic drugs, such as pergolide, have been associated with the development of cardiac valvular myxoid thickening and regurgitation in humans and more recently in rats. These effects are potentially mediated by the 5-hydroxytryptamine (5-HT)_2B receptor (5-HT_2BR). Therefore, we sought to determine whether cyproheptadine, a 5-HT_2BR antagonist, might prevent toxic valvulopathy in an animal model of pergolide-induced valvular heart disease. For this purpose, 50 male Wistar rats received daily intraperitoneal injections of pergolide (0.5 mg/kg, n = 14), pergolide (0.5 mg/kg) combined with cyproheptadine (10 mg/kg, n = 12), cyproheptadine (10 mg/kg, n = 12), or no injections (control, n = 12) for 20 wk. Echocardiography was performed blindly at baseline and at 10 and 20 wk followed by pathology. At baseline, no differences between groups were found with echocardiography. At 20 wk, aortic regurgitation was present in all pergolide-treated animals, whereas it was less frequently observed in the other groups (P < 0.0001). For the other valves, this difference was less pronounced. On histopathology, not only aortic but also mitral valves were thicker, myxoid, and exhibited more 5-HT_2BR-positive cells in pergolide-treated animals compared with the other groups. Moreover, regurgitant aortic and mitral valves were thicker than nonregurgitant aortic and mitral valves. In conclusion, we found that cyproheptadine prevented pergolide-induced valvulopathy in rats, which was associated with a reduced number of 5-HT_2BR-positive valvular cells. This may have important clinical implications for the prevention of serotonergic drug-induced valvular heart disease.

drugs; echocardiography; pathology; valves