The class III antiarrhythmic effect of sotalol exerts a reverse use-dependent positive inotropic effect in the intact canine heart
Adelqui O. Peralta, MDa,
Roy M. John, MBBS, PhD, FRCP, FACCa,
William H. Gaasch, MD, FACCa,
Peter I. Taggart, MD, FRCP*,
David T. Martin, MD, FRCP, FACCa and
Ferdinand J. Venditti, MD, FACCa
a Section of Cardiovascular Medicine and Laser Research Laboratory, Lahey Clinic Medical Center, Burlington, Massachusetts, USA
* University College, London, United Kingdom
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Figure 1 Effect of sotalol on action potential duration and left ventricular pressure transients during steady state pacing. In the baseline state, an increase in the pacing cycle length (from 400 to 1,000 ms) produced a 40% increase in the action potential duration and a reduction in peak (+)dP/dt. After sotalol, an increase in the pacing cycle length produced a greater (48%) increase in the action potential duration and the decline in (+)dP/dt was markedly attenuated. dP/dt = time derivative of pressure; PCL = pacing cycle length.
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Figure 2 Action potential duration (APD90) and left ventricular peak (+)dP/dt in steady state pacing experiments. As cycle length increased, action potential duration progressively increased in all three states. After sotalol, the APD was significantly longer than that seen during the baseline state and with esmolol (*p < 0.001; p < 0.001 for interaction). Left ventricular peak (+)dP/dt was higher with sotalol than it was with esmolol (significant at cycle lengths above 400 ms [*p < 0.001; p < 0.001 for interaction]); moreover, the inverse relation between peak (+)dP/dt and cycle length (seen in baseline and esmolol states) was abolished by sotalol.
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Figure 3 Relation between LV peak (+)dP/dt and action potential duration (APD90) during the steady state pacing experiments with sotalol and esmolol. In the sotalol experiments (left panel), there was a significant direct relation between APD and LV (+)dP/dt. By contrast, no such relation was seen in the esmolol experiments (right panel). LV = left ventricular.
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Figure 4 Action potential duration (APD90) and left ventricular peak (+)dP/dt in single test pulse (restitution) experiments. Sotalol produced a substantial increase in the plateau phase of the electrical restitution curve. The APD with sotalol (at coupling intervals exceeding 400 ms) was significantly higher than that seen in the baseline state and with esmolol (p < 0.001; p < 0.001 for interaction). During the plateau phase of the mechanical restitution curve, left ventricular (+)dP/dt with sotalol exceeded that seen with esmolol at coupling intervals exceeding 600 ms (p < 0.01).
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