Intracoronary Stem Cell Delivery to the Right Ventricle: A Preclinical Study

Clinical protocols for stem cell-based therapies are currently under development for patients with hypoplastic left heart syndrome. An ideal cell delivery method should have minimal safety risks and provide a wide distribution of cells to the nonischemic right ventricle (RV). However, the optimal strategy for stem cell delivery to the RV has yet to be explored in a preclinical model, necessary for a hypoplastic left heart syndrome trial. Human c-kit⁺ cardiac stem cells (CSCs) were delivered to healthy Yorkshire swine through the proximal right coronary artery with a stop and reflow technique. The effect of premedication with antiarrhythmic (AA) medications in this model was retrospectively reviewed, with the primary outcome of survival 2 hours after infusion. A group underwent CSC delivery to the RV without prophylactic AA medication (no AA, n = 7), whereas the second group was premedicated with a loading dose and intravenous infusion of amiodarone and lidocaine (AA, n = 13). Cardiac biopsies were obtained from each chamber to ascertain the biodistribution of CSCs. Survival was significantly greater in the prophylactic AA group compared with the group without AA (13/13 [100%] vs 1/7 [14.3%], P < 0.0001). Cardiac arrest during balloon inflation was the cause of death in each of the nonmedicated animals. In the premedicated group, 9 (69.2%) pigs experienced transient ST segment changes in the precordial leads during CSC delivery, which resolved spontaneously. Most c-kit⁺ CSCs were distributed to lateral segments of the RV free wall, consistent with the anatomical course of the right coronary artery (lateral RV, 19.2 ± 1.5 CSCs/field of view vs medial RV, 10.4 ± 1.3 CSCs/field of view, P < 0.0001). Few c-kit⁺ CSCs were identified in the right atrium, septum, or left ventricle. Prophylactic infusion of AA enhances survival in swine undergoing intracoronary delivery of human c-kit⁺ CSCs to the RV. Additionally, intracoronary delivery results in a limited biodistribution of c-kit⁺ CSCs within the RV. Human clinical protocols can be optimized by requiring infusion of AA medications before cell delivery.