Abstract 20881: Increased Peri-Infarct Calcium Alternans Underlies Spontaneous VT and Sudden Death in LQT1 Rabbits Post Myocardial Infarction
The incidence SCD in the general population correlates with prolongation of the QT interval. We investigated the mechanism by which reduced repolarization reserve may affect post myocardial infarction (MI) arrhythmias by generating MI in transgenic rabbits with type 1 long QT syndrome (LQT1), which lack I Ks but show no spontaneous or inducible arrhythmias at baseline and their littermate controls (LMC). Adult male LMC and LQT1 rabbits underwent closed chest occlusion of the mid first obtuse marginal branch of the left circumflex via microcoil delivery or sham procedure. After 3 weeks monitoring post MI, all groups underwent echocardiogram, in vivo electrophysiology study (EPS), followed by dual voltage (Vm)-calcium (Cai) epicardial optical mapping in an isolated heart preparation with the same programmed stimulation used in vivo . 15 LMC (5 sham) and 7 LQT1 (3 sham) rabbits were studied. Both MI groups demonstrated wall motion abnormality while shams did not. 2 of 4 LQT1 post MI had spontaneous ventricular arrhythmias (1 VF arrest and 1 with recurrent monomorphic VT). No spontaneous arrhythmias were seen in LMC MI or shams. At EPS, LQT1 MI rabbits were more inducible compared to LMC MIs (3/3 LQT1 vs 3/10 LMC). No shams were inducible. Optical mapping (figure below) demonstrated greater APD dispersion in LQT1 MI hearts compared to LMC MI (57±8ms vs 35±15ms; p<0.05), which supported reentry formation with programmed stimulation. Shams showed little APD dispersion (19.5±5ms LMC shams vs 22±4ms LQT1 shams). Regions of high dispersion bordering scar demonstrated beat to beat calcium transient alternans which was significantly increased in LQT1 MI compared to LMC MI (27±15% oscillation in LQT1 MI vs 6±6% in LMC MI; p=0.05). In the absence of I Ks, LQT1 rabbits post MI demonstrate greater peri-scar calcium transient alternans allowed for increased APD dispersion and reentry formation and thereby increased the propensity for spontaneous and inducible arrhythmias.
- © 2010 by American Heart Association, Inc.