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Updated: Sep 26, 2026
Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction
Published on: October 14, 2016
Effects of acute ischemia, early extrabeats and propafenone on complex activation patterns in intact and ischemic
Alexander Bauer1, Ruediger Becker, Frederik Voss
1Department of Cardiology, University of Heidelberg, Germany. alme.bauer@gmx.net <alme.bauer@gmx.net>
Insights
Sodium channel blockers like propafenone can suppress arrhythmias but may increase risks. In dogs with ischemia, propafenone reduced conduction anisotropy, paradoxically increasing conduction block and potential proarrhythmic effects.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Sodium channel blockers are used for ventricular arrhythmias but have shown increased mortality in coronary heart disease (CHD).
- These drugs are expected to reduce reentry arrhythmias by decreasing cardiac conduction anisotropy.
- In vitro studies suggest reduced excitability may paradoxically increase conduction block and reentry risk.
Purpose of the Study:
- To investigate the effects of propafenone on anisotropic conduction properties during acute myocardial ischemia in a canine model.
- To explore the relationship between propafenone-induced changes in anisotropy and the risk of conduction block and arrhythmias.
Main Methods:
- Utilized three-dimensional mapping techniques in 11 dogs to assess epicardial and transmural activation spread.
- Evaluated conduction velocities (CV) along and across myocardial fibers under baseline, ischemic, and propafenone-treated conditions.
- Compared CVs during constant and premature epicardial stimulation (PES).
Main Results:
- Baseline conduction was anisotropic, with higher velocities along than across epicardial fibers and along oblique compared to straight transmural pathways.
- Acute ischemia did not significantly alter tissue anisotropy.
- Propafenone significantly reduced epicardial and transmural anisotropy, which was associated with an increased probability of conduction block.
Conclusions:
- Propafenone demonstrated both antiarrhythmic and proarrhythmic potential in dogs with acute myocardial ischemia.
- Reduced anisotropy by propafenone may paradoxically promote conduction block, potentially explaining excessive arrhythmic death rates in CHD patients.
- Findings offer insights into the complex mechanisms underlying the adverse effects of sodium channel blockers in ischemic heart disease.
Abstract:
Although, sodium channel blockers have the ability to suppress nonsustained ventricular arrhythmias, an excessive drug-associated arrhythmic death rate has been reported in patients with coronary heart disease (CHD). Sodium channel blockers should prevent initiation of reentry activation by reducing directional differences in cardiac conduction (anisotropy). However, in vitro data demonstrated, that reduction of membrane excitability, e.g. by lowering the inward Na+ current, increases the risk for conduction failure and associated reentry arrhythmias. In 11 dogs the effects of myocardial ischemia, premature epicardial stimulation (PES) and propafenone on anisotropic conduction properties were tested using three-dimensional mapping techniques. The epicardial (longitudinal and transverse to fiber orientation) and transmural (oblique and straight) spread of activation was reconstructed during constant and PES. At baseline, conduction velocities (CV) were higher along (1.20 +/- 0.41 m/s) than across (0.91 +/- 0.19 m/s; p < 0.05) epicardial muscle fibers as well as along oblique (1.77 +/- 0.75 m/s) compared to straight (0.39 +/- 0.09 m/s, p < 0.05) transmural pathways. Acute ischemia did not significantly reduce tissue anisotropy. PES and additional administration of propafenone epicardially eliminated and transmurally profoundly reduced tissue anisotropy (longitudinal 0.58 +/- 0.09 m/s, transverse 0.69 +/- 0.08 m/s, oblique 0.69 +/- 0.28 m/s, straight 0.27 +/- 0.07 m/s). However, reduced anisotropy was associated with a higher probability for conduction block along myocardial fibers in the epicardium and along oblique transmural pathways. Our data show, that propafenone exhibits both potential pro- and antiarrhythmic effects in dogs with acute myocardial ischemia. These results possibly provide more insights in mechanisms underlying the excessive drug-associated arrhythmic death rate in patients with CHD.
