Abstract 3104: Focal Modification of the Canine Atrium by Linear Injections of Autologous Fibroblasts and TGF Beta 1
Background: Radiofrequency ablation has emerged as a highly successful method to eliminate AF, but complications from thermal injury provide the incentive to investigate other potential methods to create ablation lines. Injected fibroblasts have been shown to focally modify conduction with minimal collateral injury. We studied if the linear implantation of autologous fibroblasts, TGF beta 1 a stimulant of fibroblasts, or a combination of both would result in meaningful interruption of atrial conduction.
Methods: Skin biopsies were obtained from 12 mongrel dogs 2 weeks prior to implantation, and grown in culture. Using an 8F NOGA injection catheter under electroanatomic map guidance, 0.25 ml of resuspended cells were injected in a line along the posterior right atrium from the SVC to the IVC. 8 dogs received CM-DiI labeled fibroblasts alone (1 X 10^6 cells/ml), 8 dogs TGF beta 1 in saline, 4 dogs combined fibroblast/TGF beta 1 (1 X 10^6 cells/ml), and 4 dogs saline only. The therapy line was assessed after 4 weeks with standard (20 pole catheter) and optical methods.
Results: Each dog received 40 ml of therapy (160 injections). Regardless of therapy type, there was no immediate detectable zone of slow conduction or block along the atrial line. At 4 weeks a zone of slow conduction was detected in the atrium in 0 (0%) of the control dogs, 1 (14%) fibroblast dogs, 1 (14%) TGF beta 1 dogs, and 3 (75%) of the combination dogs. Gross continuous endocardial linear lesions were detected along the posterior wall of right atrium in all animals, without full-thickness extension to the epicardium. Optical mapping identified endocardial conduction block at the atrial line in 0 (0%) control dogs, 2 of 4 (50%) fibroblast dogs, 2 of 6 (30%) of the TGF beta 1 dogs, and 2 of 3 (66%) of the combination therapy dogs, despite incomplete atrial penetration. CM-DiI labeled fibroblast stained positive for Vimentin and were identified in all dogs that received cells.
Conclusions: Atrial conduction can be modified by linearly injected fibroblasts and TGF Beta 1 with minimal local injury. The effect on atrial myocardium of fibroblasts is enhanced by pretreatment with TGF beta 1. These data have relevant therapeutic potential for the development on novel cell-based nonpharmacologic therapies for AF.