pyrimidinones and Heart-Diseases

In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation.. Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD.. AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Drug Therapy, Combination; Electric Countershock; Emergency Service, Hospital; Female; Heart Arrest; Heart Diseases; Humans; Male; Middle Aged; Prognosis; Pyrimidinones; Survival Analysis; Treatment Outcome; Ventricular Fibrillation

Suppression of implantable defibrillator discharges associated with ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed to investigate the efficacy of intravenous nifekalant hydrochloride in predicting the effects of oral sotalol.. The present study included 14 patients who had sustained VTA associated with structural heart disease. All patients also had inducible VTA. To compare the effects of nifekalant and sotalol, programmed electrical stimulation was performed, in the basal state, after nifekalant administration, and after sotalol administration. Nifekalant and sotalol similarly prolonged the corrected QT interval and ventricular effective refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5 patients whose VTA became non-inducible by nifekalant, subsequent treatment with sotalol also suppressed the inducible VTA. In all of the 9 patients non-responding to nifekalant, VTA remained inducible during sotalol treatment. Nifekalant accurately predicted the response to sotalol during electrophysiologic study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred in 3 non-responders during a follow-up of 46 +/- 11 months.. Nifekalant and sotalol had similar effects on inducible VTA. The response of inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Drug Therapy, Combination; Electric Stimulation; Electrocardiography; Electrophysiology; Female; Heart Diseases; Humans; Male; Middle Aged; Pyrimidinones; Secondary Prevention; Sotalol; Tachycardia, Ventricular; Treatment Outcome

Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the K+ channel without inhibiting beta-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 +/- 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% +/- 49% versus 37% +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Pyrimidinones; Risk Factors; Treatment Outcome; Ventricular Fibrillation

We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.

Topics: Diseases in Twins; Electrocardiography; Female; Heart; Heart Block; Heart Diseases; HIV Protease Inhibitors; Humans; Infant, Newborn; Infant, Premature; Infectious Disease Transmission, Vertical; Lopinavir; Pyrimidinones; Ritonavir; Twins

Topics: Adult; Cardiomyopathy, Dilated; Crystallization; Echocardiography, Transesophageal; Female; Heart Diseases; Humans; Infusions, Intravenous; Potassium Channel Blockers; Pyrimidinones; Thrombosis

In experiments performed in mice, Adriamycin (15 mg/kg i. p.) produced serious damage of the heart muscle. Damvar (2 x 200 mg/kg orally) a new cytostatic drug combined with Adriamycin decreased conspicuously its cardiotoxicity.

Topics: Animals; Antineoplastic Agents; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Heart Diseases; Male; Mice; Pyrimidinones