Wednesday, January 23, 2008

Cells: The New Antiarrhythmic?

Innovative work was reported in Circulation on-line (before print) that demonstrated that genetically-enginnered rat fibrous cells that expressed an important potassium channel found in heart tissue could alter the electrophysiologic properties of neighboring cardiac cells to beat slower in culture compared to control cells, and prolong the heart tissue's refractory period (the ability for a skipped beat to re-stimulate the heart).

Rat fibroblasts (fibrous cells) were genetically engineered to express the voltage-sensitive potassium channel Kv1.3 and placed within cell cardiocyte cultures. They altered the electrophysiologic properties of neighboring cardiocytes (heart cells) by reducing (68%) the spontaneous beating frequency of the cultures compared with baseline values compared to control fibroblasts. Following this finding, the same fibroblasts were injected into pig right ventricular tissue and showed some lengthening of the myocardial refractory periods in pigs as well. While very preliminary, the authors (many of whom are affiliated with the Iraeli start-up company GeneGrafts, a Technion University incubator company) observed changes in the local ventricular electrophysiological properties that indicated the "ability of the engrafted engineered fibroblasts to survive, to integrate with host tissue, and to modulate local excitability by generation of electrotonic currents with neighboring cardiomyocytes."

While there was good evidence that the authors' proof of concept study was successful, its application to man is a long way from certain. Fibroblasts, after all, create scar and scar is inherently arrhythmogenic in myocardium. Nonetheless, the concept is intriguing as a new avenue to pursue for possible antiarrhythic therapy.


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