In vitro model of drug testing

Abstract

Valvular heart disease is a significant cause of cardiac morbidity and mortality. Fifteen years ago, there was an epidemic of FenPhen induced valvular heart disease due to overuse for weight loss [1]. Patients developed clinical findings of severe pulmonary hypertension and left-sided valve lesions similar to those of carcinoid heart disease [1-4]. Previously, we have published the in vitro and ex vivo mechanism of cellular proliferation secondary to serotonin induced valve disease [5]. The distinctive carcinoid cardiac lesions consist of deposits of fibrous tissue devoid of elastic fibers on the ventricular aspect of the tricuspid valve leaflets and on the arterial aspect of the pulmonic valve cusps. A similar lesion is found in FenPhen valve lesions except on the left side of the heart [1]. Despite the similar plaque formation on the endocardial surface of the cardiac valves in FenPhen patients, the cellular mechanism of this disease is not well known. This chapter will define a novel in vitro assay previously published [5], to determine if FenPhen has a direct effect on the valvular subendothelial cells through a mechanism of increase proliferation, which is responsible for the plaque formation found on these valves.