Nifekalant Research Articles

Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia

Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91–1.71) or long-term survival (OR: 1.00, 95% CI: 0.63–1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21–4.72) and long-term survival (OR: 1.88, 95% CI: 1.36–2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63–1.15) or long-term survival (OR: 1.25, 95% CI: 0.67–2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear.

Comparison of nifekalant and amiodarone for resuscitation after cardiopulmonary arrest due to shock-resistant ventricular fibrillation

Nifekalant (NIF) is a pure potassium channel blocker developed in Japan and it has been used widely for treating fatal ventricular tachyarrhythmia since 1999. Because intravenous amiodarone (AMD) was approved in 2007 in Japan, there have been few studies about the comparison of the efficacy of NIF and AMD for resuscitation after cardiopulmonary arrest patients due to shock-resistant ventricular fibrillation.

Difference of Class III Drug Effects after ICD Shock in Brugada Syndrome

Purpose: To compare drug effects on the spatial and transmural dispersion of repolarization (SDR and TDR) just after ICD shock between amiodarone (AMD) and nifekalant (NIF) in patients with Brugada syndrome (BS). Methods: We enrolled 22 consecutive patients with BS with ICD, and divided them into 2 groups: AMD group (N=12) and NIF group (N=10). We recorded 87-lead body surface ECGs before (CONTROL) and after only drug administration, and just after ICD shocks with and without drug. Corrected QT interval (QTc), QT peak interval (cQTp), and TDR (cTDR; QTc-cQTp) were measured. As an index of SDR, the dispersion of QTc (QTc-D) in 87 leads was measured. Results: Compared with CONTROL, QTc-D in both groups was significantly deteriorated by ICD shocks (AMD group; 85±12, 105±19 ms1⁄2, and NIF group; 79±10, 96±7 ms1⁄2, respectively, p<0.05). QTc-D with drug did not differ between with and without ICD shocks (AMD group; 91±19, 94±15 ms1⁄2, and NIF group; 80±13, 79±14 ms1⁄2, respectively). AMD did not increase cTDR. cTDR after drug with and without ICD shock in NIF group were larger than those in AMD group (NIF group; 148±24, 144±28 ms1⁄2, and AMD group; 123±29, 123±25 ms1⁄2, respectively, p<0.05). Conclusion: Both drugs suppressed the deterioration of SDR by ICD shocks. AMD may be more useful to suppress instability of repolarization just after ICD shocks.

Comparative Study of Nifekalant Versus Amiodarone for Shock-Resistant Ventricular Fibrillation in Out-of-Hospital Cardiopulmonary Arrest Patients

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.

Effects of Intravenous Nifekalant as a Lifesaving Drug for Severe Ventricular Tachyarrhythmias Complicating Acute Coronary Syndrome

Intravenous amiodarone (AMD) has been used for the treatment of ventricular tachycardia/fibrillation (VT/VF) in emergency care medicine. However, AMD acts slowly and is occasionally accompanied by hypotension and bradycardia. The antiarrhythmic effect of intravenous nifekalant (NIF) was assessed in patients with VT/VF complicating acute coronary syndrome (ACS) according to our study protocol. Among a series of 1,143 ACS patients, 41 patients who suffered sustained VT/VF were enrolled; 19 failed to respond to a preceding lidocaine (LID) injection. NIF was given first as an intravenous bolus injection (0.2 mg/kg) and then as a continuous intravenous infusion at a relatively low dose level (0.2 mg x kg(-1) x h(-1)). Sustained VT/VF was successfully inhibited by NIF in 34 patients (83%). In subgroup analysis, NIF achieved VT/VF inhibition in 79% of patients who received preceding LID and in 86% of patients who received direct NIF. There were no significant changes in systolic blood pressure or heart rate following NIF therapy. A corrected QT interval was significantly prolonged (P<0.01), whereas torsade de pointes developed in only 1 patient (2%). An intravenous bolus injection and subsequent continuous infusion of NIF at a relatively low dosage were effective in treating severe ventricular tachyarrhythmias complicating ACS, reducing the potential risk of proarrhythmia.

The Effects of Nicorandil and Nifekalant, Which Were Injected into the Pericardial Space, for Transmural Dispersion of Repolarization in the Pig

Introduction: Some studies have reported that transmural dispersion of repolarization (TDR) is involved in the onset of ventricular arrhythmia. We investigated the effects of nicorandil (NIC) and nifekalant (NIF) injected into the pericardial space, on TDR and T waves in the pig. Methods and Results: We injected NIC 4 or 8 mg and NIF 50 or 100 mg at intervals into the pericardial space for eleven pigs. The effects of these drugs were investigated on the effective refractory period (ERP) between the endocardial and epicardial myocardial cells, as well as on QT time, QT peak-end (QTcpe) as an index of TDR, and T waveforms, respectively. QTcpe increased from 91 ± 21 to 116 ± 19 msec, 2.8 min after injection of NIC (p < 0.01), although corrected QT (QTc) interval did not changed. But 5.5 min after injection, QTc decreased while QTcpe recovered. T wave amplitude significantly increased, and epicardium ERP decreased. When NIF was injected, TDR decreased from 55 ± 10 msec to 44 ± 8 msec (p < 0.01) although QTc did not change. In a later phase, QTc increased (p < 0.01) and QTcpe recovered. T wave amplitude rapidly decreased and became negative. Conclusion: Injected into the pericardial space, NIC and NIF brought about certain changes in ERP, QT and T waveform. Furthermore, NIC increased TDR while NIF decreased TDR.

The Effects of Nicorandil and Nifekalant, Which Were Injected into the Pericardial Space, for Transmural Dispersion of Repolarization in the Pig

Introduction: Some studies have reported that transmural dispersion of repolarization (TDR) is involved in the onset of ventricular arrhythmia. We investigated the effects of nicorandil (NIC) and nifekalant (NIF) injected into the pericardial space, on TDR and T waves in the pig. Methods and Results: We injected NIC 4 or 8 mg and NIF 50 or 100 mg at intervals into the pericardial space for eleven pigs. The effects of these drugs were investigated on the effective refractory period (ERP) between the endocardial and epicardial myocardial cells, as well as on QT time, QT peak‐end (QTcpe) as an index of TDR, and T waveforms, respectively. QTcpe increased from 91 ± 21 to 116 ± 19 msec, 2.8 min after injection of NIC (p &lt; 0.01), although corrected QT (QTc) interval did not changed. But 5.5 min after injection, QTc decreased while QTcpe recovered. T wave amplitude significantly increased, and epicardium ERP decreased. When NIF was injected, TDR decreased from 55 ± 10 msec to 44 ± 8 msec (p &lt; 0.01) although QTc did not change. In a later phase, QTc increased (p &lt; 0.01) and QTcpe recovered. T wave amplitude rapidly decreased and became negative. Conclusion: Injected into the pericardial space, NIC and NIF brought about certain changes in ERP, QT and T waveform. Furthermore, NIC increased TDR while NIF decreased TDR.

Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant

Nifekalant (NF) is a novel class III antiarrhythmic agent that is effective in preventing life-threatening ventricular tachycardia/fibrillation (VT/VF). We investigated mechanisms of destabilization and early termination of spiral-type reentrant VT by NF in a two-dimensional subepicardial myocardial layer of Langendorff-perfused rabbit hearts (n = 21) using a high-resolution optical action potential mapping system. During basic stimulation, NF (0.1 microM) caused uniform prolongation of action potential duration (APD) without affecting conduction velocity and an increase of APD restitution slope. VTs induced by direct current stimulation in the presence of NF were of shorter duration (VTs > 30 s: 2/54 NF vs. 19/93 control). During VTs in control (with visible rotors), the wave front chased its own tail with a certain distance (repolarized zone), and they seldom met each other. The average number of phase singularity (PS) points was 1.31 +/- 0.14 per 665 ms (n = 7). In the presence of NF, the wave front frequently encountered its own tail, causing a transient breakup of the spiral wave or sudden movement of the rotation center (spatial jump of PS). The average number of PS was increased to 1.63 +/- 0.22 per 665 ms (n = 7, P < 0.05) after NF. The mode of spontaneous termination of rotors in control was in most cases (9/10, 90.0%) the result of mutual annihilation of counterrotating wave fronts. With NF, rotors frequently terminated by wave front collision with the atrioventricular groove (12/19, 63.2%) or by trapping the spiral tip in a refractory zone (7/19, 36.8%). Destabilization and early termination of spiral wave reentry induced by NF are the result of a limited proportion of excitable tissue after modulation of repolarization.

P3-8: Destabilization and early termination of spiral-wave reentry by a class III antiarrhythmic agent, nifekalant, in a perfused 2-dimensional layer of rabbit ventricular myocardium

Nifekalant (NF) is a novel class III antiarrhythmic agent that is effective in preventing recurrent life-threatening ventricular tachycardia/fibrillation (VT/VF). However, since mechanism underlying the antiarrhythmic action of NF is unknown, we investigated the effects of NF on the dynamics of functional reentry in rabbit hearts.

Can Nifekalant Hydrochloride be Used as a First-Line Drug for Cardiopulmonary Arrest (CPA)?

Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I(Kr) blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR.

Nifekalant promotes termination of spiral-reentry by limiting the cardiac tissue proportion available for excitation: A high-resolution optical signal analysis of wave-front and wave-tail

Purpose: We showed recently that nifekalant (NF), a specific IKr blocker destabilizes spiral-reentry and facilitates its termination in two-dimensional rabbit ventricles. In this study, we investigated mechanisms of the early termination with NF by analyzing the wave-front and wave-tail dynamics.

Defibrillation Effects of Intravenous Nifekalant in Patients with Out‐of‐Hospital Ventricular Fibrillation

Nifekalant (NF), a pure K(+) channel blocker developed in Japan, has been reported to be effective in the treatment of life-threatening ventricular arrhythmias. We studied its efficacy in 18 men and 4 women with out-of-hospital ventricular fibrillation (VF) admitted to our emergency department between August 2001 and March 2004. The number of DC shocks delivered for out-of-hospital VF, serum Na(+) and K(+), arterial blood pH, and base excess were compared in 8 patients treated with NF, 0.3 mg/kg i.v. followed by a continuous intravenous (group N) versus 14 patients treated with lidocaine, 2 mg/kg, i.v. (group C). The two groups were similar with respect to their baseline characteristics. Sinus rhythm returned in 5 of 8 patients in group N versus 2 of 14 patients in group C (P < 0.05). These seven patients were admitted to the intensive care unit, though all died within 1 month. The results of this study suggest that NF may be effective in defibrillation of out-of-hospital VF, though controlled studies are needed to confirm our observations.

Effect of nifekalant for out-of–hospital cardiac arrest with shock-resistant ventricular fibrillation

Nifekalant (NIF) is predominantly a Vaughan Williams Class III antiarrhythmic agent that is synthesized in Japan as a pure K channel blocker without a negative inotropic effect [1]. NIF has been the most effective antiarrhythmic drug recommended for patients with ventricular fibrillation (VF) resistant to some other antiarrhythmic drugs in Japan. However, whether NIF improves the rate of successful resuscitation after out-of-hospital cardiac arrest with shock-resistant VF has not been determined. Our preliminary study found a significant improvement in the proportion of patients surviving to the emergency department following out-of-hospital cardiac arrest in NIF-treated patients [2]. Our protocol is as follows: for out-of-hospital cardiac arrest patients with shock-resistant VF or pulseless VT (after three or more precordial shocks), epinephrine (1 mg bolus) and then NIF (0.3 mg/kg bolus followed by 0.4 mg/kg/hour infusion) are administered. We showed 31% of out-of-hospital cardiac arrest patients with shock-resistant VF could survive by treatment with this protocol [2]. We will show the details of the clinical course of successfully recovered patients treated with this protocol.