No abstract

Cilostazol is a selective phosphodiesterase 3 (PDE3) inhibitor approved by the Food and Drug Administration for treatment of intermittent claudication. It has also been used in bradyarrhythmic patients to increase heart rates. Recently, cilostazol has been shown to prevent ventricular fibrillation in patients with Brugada syndrome. Cilostazol is hypothesized to suppress transient outward potassium (Ito) current and increase inward calcium current, thus, maintaining the dome (phase 2) of action potential, decreasing transmural dispersion of repolarization and preventing ventricular fibrillation. Although many PDE3 inhibitors have been shown to increase cardiac arrhythmia in heart failure, cilostazol has presented effects that are different from other PDE3 inhibitors, especially adenosine uptake inhibition. Owing to this effect, cilostazol could be an effective cardioprotective drug, with its beneficial effects in preventing arrhythmia. In this review, the cardiac electrophysiological effects of cilostazol are presented and its possible cardioprotective effects, particularly in preventing ventricular fibrillation, are discussed, with emphasis on the need to further verify its clinical benefits.

HRV is depressed in TM patients. HRV was significantly correlated with Hb level, suggesting that anemia greatly influences the cardiac autonomic balance.

G-CSF increases the DPT, ERP and VFT and reduces the infarct size, thus stabilizing the myocardial electrophysiology, and preventing fatal arrhythmia during I/R. The protective mechanism could be via its effect in preventing cardiac mitochondrial dysfunction.

We have studied the spatiotemporal pattern of blebbistatin-induced anomalous electrical activities in isolated rat atrial preparations using the optical mapping of excitation spread. Atrial preparations including the right or left auricle were dissected from adult rat hearts. Each preparation was then stained with a fast merocyanine-rhodanine voltage-sensitive dye (NK2761). Using a multi-element (16 x 16) photodiode array, we assessed the spread of excitation optically by timing the initiation of the action potential-related extrinsic absorption changes. The contraction-related optical signals were suppressed by adding (S)-(-)-blebbistatin (10-100 miocroM) to the bathing solution. Blebbistatin had an effective delay time of about 1.5 h following its application, at which time anomalous electrical activities occurred. These took the form of triggered activities and rhythmical spontaneous excitations. We optically mapped the spatiotemporal patterns of the excitation spread during these anomalous electrical activities. When the triggered activities occurred, the site of ectopic focus, where the triggered action potential first appeared, and the area of excitation spread varied in every event. When the rhythmical spontaneous excitations occurred, the excitation spread from the anomalous pacemaker and, occasionally, their spatial shift was observed. In addition, the combination pattern of the spontaneous excitations and triggered activities was also observed. We suggest that these phenomena are due to the disturbed intracellular calcium dynamics induced by the application of blebbistatin.

No abstract

Previous reports demonstrated that cilostazol, a phosphodiesterase 3 inhibitor, affected cellular electrophysiology and reduced episodes of ventricular fibrillation (VF) in patients with Brugada syndrome. However, its effects on VF induction and defibrillation efficacy have never been investigated. We tested the hypothesis that cilostazol increases the VF threshold (VFT) and decreases the upper limit of vulnerability (ULV) and the defibrillation threshold (DFT). A total of 48 pigs were randomly assigned to defibrillation and VF induction studies. The diastolic pacing threshold (DPT), VFT, ULV, DFT, and effective refractory period were determined before and after the infusion of cilostazol at 6 mg/kg, 3 mg/kg, or vehicle. The DPT was significantly increased after administration of 3 and 6 mg/kg cilostazol. The ULV and DFT were significantly decreased after administration of 6 mg/kg cilostazol only. The ULV in the 6 mg/kg group had 12% lower peak voltage and 25% lower total energy, and the DFT had 13% lower peak voltage and 25% lower total energy. The VFT was not altered in any experimental group. This study shows that cilostazol administration significantly increased the DPT, which was associated with significantly reduced DFT and ULV.