Abstract 16485: Viral and Cell Delivery of SkM1 in the Post Infarct Period Have Differing Effects on Arrhythmia Induction
Introduction: In the depolarized myocardial infarct epicardial border zone (EBZ), the cardiac sodium channel is largely inactivated and contributes to the low action potential upstroke velocity (Vmax), slow conduction and reentry. We have previously demonstrated that adenoviral overexpression of the skeletal muscle sodium channel SkM1 in the EBZ can normalize conduction and reduce the induction of ventricular tachycardia or fibrillation (VT/VF). We now studied the effect of cell delivery of SkM1 to the EBZ using canine mesenchymal stem cells (cMSC).
Methods: Canine myocardial infarcts were created by LAD ligation and animals were divided into 3 groups: 1) sham (Ad-GFP injected or non-injected; n=20) 2) unloaded cMSC (cMSC; n=10) and 3) cMSC loaded with SkM1 (cMSC/SkM1; n=10). Injections were made into EBZ immediately after LAD ligation. One week later, dogs were studied by programmed electrical stimulation (PES) in vivo and cellular electrophysiology in vitro .
Results: In vivo, EBZ electrograms were broad and fragmented in sham (29±0.3 ms) and cMSC (27±1.5 ms) and narrower in cMSC/SkM1 (21±1.7 ms; P <.05 vs. sham and cMSC). ANOVA of microelectrode studies of EBZ from SkM1 animals showed increased Vmax – MDP curves compared to sham and cMSC (see figure; P <.05). Yet despite these potentially therapeutic actions, PES induced VT/VF >30 seconds in 12 of 20 sham, 3 of 10 cMSC and 7 of 10 cMSC-SkM1 (P>.05). Mean infarct size was 29±1.4% and did not differ among groups (P >.05), suggesting that infarct heterogeneity among groups was not a factor here. However, heterogeneously distributed cMSC-SkM1 in the EBZ was demonstrated using immunohistochemistry.
Conclusions: The effects of cMSC/SkM1 administration on Vmax and EG characteristics in the EBZ were identical to what we reported earlier for adenoviral SkM1 administration, but the antiarrhythmic action of SkM1 was lost. We hypothesize this loss of effect may relate to the relatively heterogeneous distribution of the cMSC-SkM1.
- © 2010 by American Heart Association, Inc.