ABSTRACT
We examined the electrophysiological effects of trapidil on the ionic currents influencing the repolarization and on the transient inward current (ITi) that can cause triggered arrhythmia using the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Trapidil shortened the action potential duration (APD) and increased the delayed rectifier potassium current (IK) in a concentration-dependent manner. The effect of trapidil on the rapidly and slowly activating components of IK (IKr and IKs, respectively) was studied by the envelope of tails test. Trapidil failed to affect IKr and selectively enhanced IKs. Trapidil increased the amplitude of the L-type Ca2+ current (ICa,L), with an acceleration of its inactivation, whereas isoproterenol, a beta-adrenoceptor agonist, increased the amplitude of the ICa,L in a different manner. Isoproterenol activated ITi; however, trapidil not only failed to facilitate ITi but also suppressed isoproterenol-induced ITi. The inhibitory effect of trapidil on isoproterenol-induced ITi is at least partly via a reduction of Ca2+ overload through an acceleration of ICa,L inactivation and/or a sarcoplasmic reticulum (SR) Ca channel modulation. These results suggest that trapidil does not prolong the QT interval and has an antiarrhythmic effect on arrhythmias elicited by triggered activity secondary to Ca2+ overload at much higher concentrations than clinical concentration.
Subject(s)
Action Potentials/drug effects , Heart Ventricles/cytology , Myocytes, Cardiac/drug effects , Potassium Channels, Inwardly Rectifying/metabolism , Potassium/metabolism , Trapidil/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Calcium Channels, L-Type/metabolism , Catecholamines/pharmacology , Dose-Response Relationship, Drug , Guinea Pigs , In Vitro Techniques , Isoproterenol/pharmacology , Male , Microelectrodes , Myocytes, Cardiac/physiology , Patch-Clamp Techniques , Ryanodine/pharmacologyABSTRACT
Chondrosarcoma is a malignant tumor characterized by the formation of cartilage. A case of primary cardiac chondrosarcoma of the left atrium developed in a middle-aged male. The preoperative serum concentrations of C-parathyroid hormone-related protein (PTHrP) and calcium were high (413.2 pmol/L and 12.2 mg/dl, respectively), but normalized after resection of the tumor, which measured 7 x 5 x 3.5 cm. The tumor was histopathologically diagnosed as chondrosarcoma, composed of outer atypical chondroid cells and inner pleomorphic and spindle mesenchymal cells mimicking malignant fibrous histiocytoma. Half of the cartilaginous tumor cells and a few pleomorphic cells showed cytoplasmic immunoreactivity for PTHrP. The tumor is a possible example of the functional pleiotropy of chondrosarcoma.
