Abstract 16005: Correlation Between Spatial Differences in Action Potential Duration and Diastolic Dysfunction in Transgenic LQT2 Rabbits
Introduction: Enhanced dispersion of action potential duration (APD) due to heterogeneous prolongation of cardiac repolarization is a major contributor to Long-QT syndrome (LQTS)-related arrhythmias. We have tested the hypothesis that regional differences in cardiac repolarization correlate with regional differences in mechanical function using transgenic LQT2 rabbits.
Methods: Adult female transgenic LQT2 rabbits and wildtype littermate controls (n=7, each) were subjected to in vivo phase contrast MRI in a 1.5T MR-system under ketamine/xylazine anesthesia to assess regional systolic and diastolic radial, rotational, and longitudinal velocities (Vr, Vrot, Vz) in the left ventricle (LV, AHA 16 segment model). The same rabbits' hearts were subsequently Langendorff-perfused and subjected to ex vivo epicardial monophasic action potential measurements to assess APD in the corresponding segments.
Results: APD was significantly longer in LQT2 than in LMC rabbits in all segments of the LV (Fig. A, p<0.01 each). Peak diastolic Vr was reduced in LQT2 as compared to LMC in basal and mid LV (Vr_basal, cm/s, LQT2 -3.52±0.4 vs. LMC -4.54±0.4, p=0.001; Vr_mid, LQT2 -2.69±0.3 vs. LMC -4.67±0.8, p<0.001) - indicating an impaired diastolic function in LQT2 rabbits. Moreover, spatial APD dispersion was significantly greater (SD of APD, ms, LQT2 14.06±3.3 vs. LMC 9.32±4, p<0.05) and regional differences in peak diastolic Vr were more pronounced in LQT2 than in LMC rabbits (SD of regional Vr_mid, cm/s, LQT2 2.37±0.24 vs. LMC 1.23±0.31, p<0.001, Fig. B, C). In LQT2, APD correlated with peak diastolic Vr and Vz in basal LV segments (Vr, CC 0.47, p=0.013; Vz, CC 0.44, p=0.019).
Conclusions: Prolongation of cardiac repolarization leads to impaired diastolic function in transgenic LQT2 rabbits. Moreover, regional differences in APD correlate with regional diastolic function indicating that LQTS is not purely an electrical but rather an electromechanical disorder.
- © 2011 by American Heart Association, Inc.