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

Characteristics of head-up tilt testing with additional adenosine compared with head-up tilt testing with isoproterenol and isosorbide dinitrate

Background: Head-up tilt (HUT) testing is used to establish the diagnosis of neurally mediated syncope (NMS). Adenosine administration during HUT testing is useful for inducing NMS. However, no comparison between adenosine HUT testing and HUT testing using other drugs has been reported. The purpose of this study was to investigate the clinical usefulness of adenosine compared with isoproterenol (ISP) and isosorbide (ISDN) during HUT testing. Methods: The subjects comprised 103 consecutive patients with unexplained syncope who underwent adenosine and isoproterenol (ISP) HUT tests following a negative response in a drug-free HUT test. Subjects were first tilted upright at an 80° angle for 30 min and shown to have a negative response in drug-free HUT test. Subsequently, a continuous bolus of 0.1- or 0.2-mg/kg adenosine was administered while the subjects remained upright and were observed for 5 min (adenosine HUT test). Next, they were tilted upright for 15 min during a continuous infusion of 0.01–0.02 mg/kg min ISP (ISP HUT test). Lastly, they were tilted upright for 15 min after 1.25-mg ISDN infusion (ISDN HUT test). Results: The diagnostic yield of the adenosine HUT test was 18.1% (18/99) and that of the ISP HUT test was 6.0% (6/99; p=N.S.). Sixty-one of 99 patients underwent ISDN HUT testing, and 17 patients had a positive response. The diagnostic yield of the adenosine HUT test was 14.7% (9/61) and that of ISDN HUT test was 27.8% (p<0.05). Five patients had positive responses in both adenosine and ISDN HUT tests. Conversely, 4 patients had a positive response in the adenosine HUT test and a negative response in the ISDN HUT test. Conclusion: The adenosine HUT test was effective in the diagnosis of NMS and is useful as the ISP HUT test for inducing NMS. The diagnostic yield of the adenosine HUT test was not higher than that of the ISDN HUT test. However, the adenosine HUT test took only a few minutes and induced NMS in some of the patients in whom NMS was not induced by the ISDN HUT test. Therefore, performing adenosine HUT testing is worthwhile

Electrical Remodeling in Persistent Atrial Fibrillation May Be Mediated by Changes in the IKATP Channel

The goal of this study was to measure the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) after cardioversion in patients with persistent atria] fibrillation (AF) and to determine the effects of the adenosine triphosphate sensitive potassium channel (KATP) opening agent, nicorandil, on those parameters in patients with persistent AF. METHODS: Patients with AF underwent elective cardioversion followed by measurement of ERP and CV before and after administration of nicorandil. Parameters were measured again one week later, and the ERP and the CV was used to calculate WL. RESULTS: ERP was significantly shorter immediately after termination of AF than at the 1-week time point (193.4 vs. 228.7 msec p < 0.01). While there was no significant difference in ERP immediately after termination of AF when comparing measurements taken before and after the administration of nicorandil, ERP at the 1-week time point was shorter after nicorandil administration than before nicorandil administration (193.4 vs. 191.4 msec, n.s.; 228.7 vs. 217.2msec, p < 0.01). Further, WL was higher at the 1-week time point after nicorandil administration than before nicorandil administration. CONCLUSIONS: These data indicate that the electrical remodeling that occurs after cardioversion is at least partially mediated by changes in KATP channel behavior. Further, the electrophysiologic properties, that is, nicorandil prolonging the WL, may be of benefit in reducing the recurrence rate of AF