Harumichi Nakagawa

Moderate hypothermia increases the chance of spiral wave collision in favor of self-termination of ventricular tachycardia/fibrillation

In cardiac arrest due to ventricular fibrillation (VF), moderate hypothermia (MH, 33 degrees C) has been shown to improve defibrillation success compared with normothermia (NR, 37 degrees C) and severe hypothermia (SH, 30 degrees C). The underlying mechanisms remain unclear. We hypothesized that MH might prevent reentrant excitations rotating around functional obstacles (rotors) that are responsible for the genesis of VF. In two-dimensional Langendorff-perfused rabbit hearts prepared by cryoablation (n = 13), action potential signals were recorded by a high-resolution optical mapping system. During basic stimulation (2.5-5.0 Hz), MH and SH caused significant prolongation of action potential duration and significant reduction of conduction velocity. Wavelength was unchanged at MH, whereas it was shortened significantly at SH at higher stimulation frequencies (4.0-5.0 Hz). The duration of direct current stimulation-induced ventricular tachycardia (VT)/VF was reduced dramatically at MH compared with NR and SH. The spiral wave (SW) excitations documented during VT at NR were by and large organized, whereas those during VT/VF at MH and SH were characterized by disorganization with frequent breakup. Phase maps during VT/VF at MH showed a higher incidence of SW collision (mutual annihilation or exit from the anatomical boundaries), which caused a temporal disappearance of phase singularity points (PS-0), compared with that at NR and SH. There was an inverse relation between PS-0 period in the observation area and VT/VF duration. MH data points were located in a longer PS-0 period and a shorter VT/VF duration zone compared with SH. MH causes a modification of SW dynamics, leading to an increase in the chance of SW collision in favor of self-termination of VT/VF.

Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium.

BACKGROUND Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. OBJECTIVE We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (I(Na) and I(Ca,L)), respectively, on SW reentry. METHODS A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. RESULTS During constant stimulation, pilsicainide (3-5 microM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 microM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% +/- 9% for 5 microM pilsicainide vs. 22% +/- 9% for controls and 62% +/- 10% for 3 microM verapamil vs. 22% +/- 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 microM pilsicainide and 3 microM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% +/- 2% vs. 29% +/- 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. CONCLUSION Blockade of either I(Na) or I(Ca,L) stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.

Acute amiodarone promotes drift and early termination of spiral wave re-entry

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 μM) caused prolongation of action potential duration (APD) by 5.6%–9.1%, whereas lidocaine (15 μM) caused APD shortening by 5.0%–6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.