Key result
Delivery of the skeletal muscle Na+ channel via canine mesenchymal stem cells shortened QRS duration but did not reduce the induction of ventricular tachycardia or fibrillation (P>0.05).
Why the study?
Does delivery of SkM1 via cMSCs improve cardiac conduction and prevent arrhythmia induction in a canine myocardial infarct model?
Does delivery of SkM1 via cMSCs improve cardiac conduction and prevent arrhythmia induction in a canine myocardial infarct model?
p-value: p=>0.05
While cMSC-delivered SkM1 improves conduction in the infarct border zone, it fails to reduce arrhythmia induction, contrasting with previous viral gene delivery results and emphasizing the role of the delivery platform.
cMSC-delivered SkM1 may enhance conduction without antiarrhythmic benefit in infarct models; leaves open platform-specific efficacy versus prior viral approaches.
BACKGROUND: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na(+) channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1. METHODS AND RESULTS: cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (P<0.05). During programmed electrical stimulation of epicardial border zones, QRS duration in cMSC/SkM1 was shorter than in cMSC and sham (P<0.05). Programmed electrical stimulation-induced ventricular tachycardia/ventricular fibrillation was equivalent in all groups (P>0.05). CONCLUSION: cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy.
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Boink et al. (2012) studied Myocardial infarct (canine model). cMSC/SkM1 (canine mesenchymal stem cells transfected with skeletal muscle Na+ channel) vs. Sham and cMSC alone was evaluated on Programmed electrical stimulation-induced ventricular tachycardia/ventricular fibrillation (p=>0.05). Delivery of the skeletal muscle Na+ channel via canine mesenchymal stem cells shortened QRS duration but did not reduce the induction of ventricular tachycardia or fibrillation (P>0.05).
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