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 effects of sildenafil (Viagra), a specific inhibitor of phosphodiesterase 5, on ischemic myocardium was examined using an isolated rat heart model. Rats were pretreated with sildenafil at doses ranging from 0.001 mg to 0.5 mg/kg body weight. After 60 min, isolated hearts were subjected to ischemia for 30 min followed by 2 h of reperfusion. The results demonstrated that at 0.05 mg/kg (and to some extent at 0.01 mg/kg), sildenafil provided significant cardioprotection as evidenced by improved ventricular recovery, a reduced incidence of ventricular fibrillation and decreased myocardial infarction. At higher doses, it caused a significant increase in the incidence of ventricular fibrillation while at very low doses it had no effect on cardiac function. As expected, sildenafil increased cyclic 3',5'-monophosphate (cGMP) content in the heart. The results demonstrate for the first time that within a narrow dose range, sildenafil can protect the heart from ischemia/reperfusion injury, probably through a cGMP-signaling pathway.
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PMID:Cardioprotection with sildenafil, a selective inhibitor of cyclic 3',5'-monophosphate-specific phosphodiesterase 5. 1277 74

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

A 42-year-old diabetic man was admitted with systolic heart failure and pulmonary hypertension being treated with sildenafil for the previous year. With an increase in creatinine, he experienced 3 episodes of ventricular tachycardia and ventricular fibrillation. Withdrawal of the phosphodiesterase (PDE) inhibitor resulted in no further episodes of dysrhythmias. The basic pharmacology of PDE inhibitors is presented and the use of PDE-3 inhibitors for the treatment of heart failure causing an increase in sudden death is also reviewed. There have been several cases of sudden death associated with sildenafil use and with its increasing use in patients with severe pulmonary hypertension and decompensated heart failure. The authors also reviewed the electrophysiologic effects of PDE-5 inhibitors associated with their use. The crossover between PDE-3 and PDE-5 inhibitors is also discussed and caution is urged when contemplating the use of PDE-5 inhibitors in patients with systolic heart failure and pulmonary hypertension.
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PMID:Phosphodiesterase inhibitors, congestive heart failure, and sudden death: time for re-evaluation. 2250 98

There is little information on the perioperative management of patients with dilated cardiomyopathy (DCM) undergoing non-cardiac surgery. The presence of a history or signs of heart failure and un-diagnosed DCM preoperatively, may be associated with an increased risk during non-cardiac surgery. In these patients, preoperative assessment of LV function, including echocardiography, and assessment of an individual's capacity to perform a spectrum of common daily tasks may be recommended to quantify the severity of systolic function. It is important to prevent low cardiac output and arrhythmia for the perioperative management of patients with DCM. Sympathetic hyperactivity often causes atrial or ventricular tachyarrhythmia, which could worsen systemic hemodynamics in these patients. In particular, the prevention of life-threatening arrhythmia, such as, ventricular tachycardia or ventricular fibrillation is important. To prevent perioperative low output syndrome, inotropic support, using catecholamines or phosphodiesterase inhibitors with or without vasodilators should be performed under careful monitoring. It is desirable to use a pulmonary-artery catheter during moderate to high risk surgery, because the optimum level of left ventricular pre-load is very narrow in these patients. Every effort must be made to detect postoperative heart failure by careful monitoring, including PAC, and physical examination.
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PMID:[Anesthetic management of patients with dilated cardiomyopathy undergoing non-cardiac surgery]. 2455 28

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.
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PMID:Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System. 2656 34


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