Nifekalant Hydrochloride Administration During Cardiopulmonary Resuscitation Improves the Transmural Dispersion of Myocardial Repolarization Experimental Study in a Canine Model of Cardiopulmonary Arrest

Abstract

ifekalant hydrochloride (NIF) is the first class III anti-arrhythmic agent for intravenous use covered by National Health Insurance in Japan for refractory ventricular tachycardia and fibrillation (VT/VF). NIF blocks the delayed rectifier K + channels, especially the IKr channels. NIF also has some potential to block the inward rectifier K + current IK1 and transient outward K + channel Ito. Thus it prolongs the action potential duration (APD) and stops VT/VF by extending the refractory period. 1,2 However, amiodarone (AMD) is a known K-channel blocker that also has Na blocking action and blocking action. The properties of NIF differ greatly from those of AMD.In 1999, our coworkers Tanabe et al investigated the effect of NIF (MS-551) on the effective refractory period (ERP) in the epicardium and endocardium in a canine model of acute myocardial infarction (AMI), and reported that NIF significantly prolonged the ERP in both the normal zone (NZ) and ischemic zone (IZ) of the ischemic myocardium; however, the dispersion of the ERP in the epicardium and endocardium increased in the NZ but decreased in the IZ. 3 Recently, our coworkers Amino et al conducted a comparative investigation of the 90% APD (APD90) prolonging effect of NIF on the surface of the left ventricle (LV) and APD90 dispersion (APDD) in isolated perfused rabbit hearts at basic cycle lengths (BCLs) of 400 ms and 250 ms. APD90 was prolonged with the efficacy of a reverse use dependent block without increasing the APDD at either BCL, and as a result NIF decreased VT/VF vulnerability. 4 These study results suggest that NIF may stop VT/VF by improving epicardial surface and transmural dispersion of repolarization (TDR) in the LV, in addition to its refractory-period-prolonging action.In a clinical study, we used NIF to treat lidocaine-resistant VT/VF in patients with out-of-hospital cardiopulmonary arrest (OHCPA), and reported that it exerted excellent anti-arrhythmic efficacy. 5 In a study in which we compared OHCPA patients with acidosis and in-hospital cardiopulmonary arrest (IHCPA) patients without acidosis, NIF was Background Because nifekalant hydrochloride (NIF) displayed a superior defibrillating effect on ventricular tachycardia/fibrillation (VT/VF) in cardiopulmonary arrest (CPA) patients, despite some QT prolongation, its effect on transmural dispersion of repolarization (TDR) in the left ventricle (LV) in an animal model of CPA was investigated. Methods and ResultsEight beagle dogs were created with a myocardial infarction under anesthesia, and then VT/VF induction by continuous stimulation and cardiopulmonary resuscitation (CPR) were repeated. NIF (0.3 mg/kg) was administered under acidotic conditions (pH 7.26). The QTc interval measured by Y-lead ECG showed no significant prolongation before and after NIF. The activation recovery interval (ARI) measured by 64-lead LV surface mapping showed minimum ARI prolongation (40%) by NIF without maximum ARI prolongation, and as a result the ARI dispersion decreased by 67%. The repolarization time (RPT)...

Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction

“…In-vivo electrophysiology experiments were conducted following open thorax surgery under anesthesia (α-chloralose, 80 mg/kg and urethane, 1000 mg/kg) [10]. An array of 8 × 8 monopolar electrodes (64Map) to cover 7 × 7 mm square (interpolar distance, 1 mm) was put on the LV wall between the left anterior descending branch (LAD) and left circumflex branch (LCx) of coronary arteries (Fig.…”

“…An array of 8 × 8 monopolar electrodes (64Map) to cover 7 × 7 mm square (interpolar distance, 1 mm) was put on the LV wall between the left anterior descending branch (LAD) and left circumflex branch (LCx) of coronary arteries (Fig. 5A) [10]. The 64Map signals recorded simultaneously were acquired and processed by a computer.…”

Effect of nifekalant on life-threatening ventricular arrhythmias in patients with cardiopulmonary resuscitation or during the perioperative state

“…In contrast, the shortening of action potential duration and transmural dispersion are considered to play a role in acute ischemia, and the effect of nifekalant in prolonging the action potential and decreasing transmural dispersion would be more effective in such cases. 16) In the electrocardiographic parameters, the QTc interval was significantly prolonged by nifekelant and the degree of the QTC prolongation was greater in the effective group than in the non-effective group (Figure). That result indicated that the QTc prolongation caused by the nifekalant may vary in individual patients even with the same amount of the drug, and more effective results would be expected in patients with a larger QTc prolongation.…”

Actual treatments for out‐of‐hospital ventricular fibrillation at critical care medical centers in Osaka: a pilot descriptive study

“…Two prospective randomized studies showed that use of amiodarone improved survival until hospital admission, and amiodarone became a first-line anti-arrhythmic agent for refractory VF/pulseless VT. 23,24 In Japan, nifekalant, another class III anti-arrhythmic agent for refractory VT and VF, has been available since 1999, and some studies have indicated its effectiveness in emergency settings. 25,26 Further studies into what kind of anti-arrhythmic agent would be effective for shock-resistant VF should be undertaken.…”