Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of 67-year-old man with Brugada syndrome, in whom daily episodes of ventricular fibrillation (VF) occurred every early morning for 4 days. The episodes of VF were completely prevented by an oral administration of cilostazol, a phosphodiesterase inhibitor. This effect was confirmed by the on-and-off challenge test, in which discontinuation of the drug resulted in recurrence of VF and resumption of the drug again prevented VF. This effect may be related to the suppression of I(to) secondary to the increase in heart rate and/or to an increase in Ca2+ current (I(Ca)) due to an elevation of intracellular cyclic AMP concentration via inhibition of phosphodiesterase activity. This drug might have an anti-VF potential in patients with Brugada syndrome.
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PMID:Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome. 1213 96

The ECG appearance in Brugada syndrome is caused by failure of the dome of the action potential to develop. Increased activity of the I(to) current in epicardial cells generates a transmural gradient with repolarization dispersion between the epicardium and the endocardium in the right ventricular wall, thus favoring the development of VF by a phase 2 reentry mechanism. The efficacy of cilostazol for the management of these arrhythmias has been reported. This drug is a phosphodiesterase inhibitor with positive chronotropic properties, thus blocking outward potassium currents I(to) in the myocardial tissue. We present a patient with Brugada syndrome with an implantable cardioverter defibrillator (ICD), who suffered multiple ICD discharges due to VF during therapy with this drug.
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PMID:Failure of cilostazol in the prevention of ventricular fibrillation in a patient with Brugada syndrome. 1653 60

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.
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PMID:Cilostazol attenuates ventricular arrhythmia induction and improves defibrillation efficacy in swine. 2055 10

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.
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PMID:Effects of cilostazol in the heart. 2120 Mar 26