Cyproheptadine prevents pergolide-induced valvulopathy in rats: an echocardiographic and histopathological study.
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(2B)R). Therefore, we sought to determine whether cyproheptadine, a 5-HT(2B)R 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(2B)R-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(2B)R-positive valvular cells. This may have important clinical implications for the prevention of serotonergic drug-induced valvular heart disease.
Departmnet of Cardiology, Universitair Ziekenhuis Brussel, Brussels 1090, Belgium. steven_droogmans@yahoo.com
Steven
S
Droogmans
Bram
B
Roosens
Bernard
B
Cosyns
Céline
C
Degaillier
Sophie
S
Hernot
Caroline
C
Weytjens
Christian
C
Garbar
Vicky
V
Caveliers
Miriam
M
Pipeleers-Marichal
Philippe R
PR
Franken
Tony
T
Lahoutte
Danny
D
Schoors
Guy
G
Van Camp
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000633:toxicity; D004347:Drug Interactions; D004452:Echocardiography; D005355:Fibrosis; D006349:Heart Valve Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D006351:Heart Valves / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D010479:Pergolide / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*
D018491:Dopamine Agonists; D012702:Serotonin Antagonists; D010479:Pergolide; D003533:Cyproheptadine