J Korean Med Sci.  2011 Dec;26(12):1576-1581. 10.3346/jkms.2011.26.12.1576.

Role of the Alternans of Action Potential Duration and Aconitine-Induced Arrhythmias in Isolated Rabbit Hearts

Affiliations
  • 1Department of Cardiology, Fatima General Hospital, Daegu, Korea.
  • 2Cardiovascular Division, Internal Medicine, Aging-Associated Vascular Disease Research Center, Yeungnam University Medical Center, Daegu, Korea. dgshin@med.yu.ac.kr
  • 3Cardiovascular Department, Kyungpook National University, Daegu, Korea.
  • 4Cardiovascular Division, Internal Medicine, Keimyumg University, Daegu, Korea.
  • 5Cardiovascular Division, Department of Internal Medicine, Daegu Catholic University, Daegu, Korea.

Abstract

Under conditions of Na+ channel hyperactivation with aconitine, the changes in action potential duration (APD) and the restitution characteristics have not been well defined in the context of aconitine-induced arrhythmogenesis. Optical mapping of voltage using RH237 was performed with eight extracted rabbit hearts that were perfused using the Langendorff system. The characteristics of APD restitution were assessed using the steady-state pacing protocol at baseline and 0.1 microM aconitine concentration. In addition, pseudo-ECG was analyzed at baseline, and with 0.1 and 1.0 microM of aconitine infusion respectively. Triggered activity was not shown in dose of 0.1 microM aconitine but overtly presented in 1.0 microM of aconitine. The slopes of the dynamic APD restitution curves were significantly steeper with 0.1 microM of aconitine than at baseline. With aconitine administration, the cycle length of initiation of APD alternans was significantly longer than at baseline (287.5 +/- 9.6 vs 247.5 +/- 15.0 msec, P = 0.016). The functional reentry following regional conduction block appears with the progression of APD alternans. Ventricular fibrillation is induced reproducibly at pacing cycle length showing a 2:1 conduction block. Low-dose aconitine produces arrhythmogenesis at an increasing restitution slope with APD alternans as well as regional conduction block that proceeds to functional reentry.

Keyword

Aconitine; Optical mapping; APD restitution; APD alternans

MeSH Terms

Aconitine/*pharmacology
Action Potentials/*drug effects
Animals
Arrhythmias, Cardiac/*chemically induced/*physiopathology
Cardiac Pacing, Artificial
Electrocardiography
Heart/physiopathology
Heart Conduction System/physiology
Myocardium/*pathology
Rabbits
Sodium Channels/drug effects/metabolism
Ventricular Fibrillation/physiopathology

Figure

  • Fig. 1 Pseudo-ECG findings according to the changes of aconitine concentration. From baseline (A), the heart rates were gradually accelerated depending on the concentration of aconitine (B, C) with sequential prolongation of the QT interval. With 1.0 µM of aconitine (C), humps at the terminal portion of the T-waves (open arrow) were observed suggesting early afterdepolarization representing PVCs (D: closed arrow), which progressed to ventricular bigeminy (E) and VT (F: lined arrows point the alternans of T-wave). Finally VF was initiated (G).

  • Fig. 2 Effects of aconitine on the changes of epicardial membrane potential. Administration of 0.1 µM aconitine (B) caused APD alternans at a longer pacing cycle length, with APD prolongation compared to the baseline study (A). The arrows indicate intermittent 2:1 conduction block induced VF (lower part of B).

  • Fig. 3 The patterns of wave propagation during initiation of VF after administration of 1 µM aconitine. The panel (A) shows the paced wave propagated from the LV apex to the base (A to D). The panel (B) shows that the paced wave was not propagated toward the "a" direction (regional block) whereas the wave propagated toward the "b" direction initiated VF (E to I). The electrogram (C) shows the second paced wave (dotted arrow) failed to conduct totally while the forth wave succeeded and the sixth wave was conducted with the regional block C as shown in the middle panel.

  • Fig. 4 A representative example of the dynamic APD restitution curve. The dynamic APD restitution curves and it's restitution slope at baseline (A) and after administration of 0.1 µM aconitine (B); this was steeper than at baseline (A) and prone to arrhythmogenesis.


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