{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:00:13Z","timestamp":1772164813974,"version":"3.50.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2008,2,12]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Traditional antiarrhythmic pharmacological therapies are limited by their global cardiac action, low efficacy, and significant proarrhythmic effects. We present a novel approach for the modification of the myocardial electrophysiological substrate using cell grafts genetically engineered to express specific ionic channels.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    To test the aforementioned concept, we performed ex vivo, in vivo, and computer simulation studies to determine the ability of fibroblasts transfected to express the voltage-sensitive potassium channel Kv1.3 to modify the local myocardial excitable properties. Coculturing of the transfected fibroblasts with neonatal rat ventricular myocyte cultures resulted in a significant reduction (68%) in the spontaneous beating frequency of the cultures compared with baseline values and cocultures seeded with naive fibroblasts. In vivo grafting of the transfected fibroblasts in the rat ventricular myocardium significantly prolonged the local effective refractory period from an initial value of 84\u00b18 ms (cycle length, 200 ms) to 154\u00b113 ms (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). Margatoxin partially reversed this effect (effective refractory period, 117\u00b18 ms;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). In contrast, effective refractory period did not change in nontransplanted sites (86\u00b17 ms) and was only mildly increased in the animals injected with wild-type fibroblasts (73\u00b15 to 88\u00b14 ms;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Similar effective refractory period prolongation also was found during slower pacing drives (cycle length, 350 to 500 ms) after transplantation of the potassium channels expressing fibroblasts (Kv1.3 and Kir2.1) in pigs. Computer modeling studies confirmed the in vivo results.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Genetically engineered cell grafts, transfected to express potassium channels, can couple with host cardiomyocytes and alter the local myocardial electrophysiological properties by reducing cardiac automaticity and prolonging refractoriness.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.106.671776","type":"journal-article","created":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T21:07:19Z","timestamp":1201036039000},"page":"720-731","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Cell Therapy for Modification of the Myocardial Electrophysiological Substrate"],"prefix":"10.1161","volume":"117","author":[{"given":"Lior","family":"Yankelson","sequence":"first","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yair","family":"Feld","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tal","family":"Bressler-Stramer","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilanit","family":"Itzhaki","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irit","family":"Huber","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira","family":"Gepstein","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doron","family":"Aronson","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimon","family":"Marom","sequence":"additional","affiliation":[{"name":"From the Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine (L.Y., Y.F., T.B.-S., I.I., I.H., A.G., L.G.), Minerva Center for Cell Biophysics (S.M.), and the Cardiology Department (Rambam Medical Center) (D.A., L.G.), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 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