Publications
Enhanced Local Uptake of Genetic Material Through Intramyocardial Electroporation with Helix Infusion Electrode
Mehrdad Rezaee MD, Hardwin Mead MD, Jay Wohlgemuth MD, Thomas Quertermous MD, Daniel Rosenman, Peter Altman
Stanford University, BioCardia Inc.
Intramyocardial gene therapy for local myocardial treatment is currently under
clinical evaluation. However, the optimal system for most efficacious delivery
has not been established. In order to enhance efficacy, electrical stimulation
to augment cellular uptake of genetic material after intramyocardial delivery
(IMD) has been evaluated. In order to circumvent the potential for inducing
arrhythmias during electrical stimulation, a novel intramyocardial
electroporation catheter system has been developed. The catheter tip contains a
hollow helical needle geometrically similar to electrodes used in active
fixation intramyocardial pacing leads. The safety and feasibility of this system
was established first as a helix infusion system for IMD. In 30 consecutive pigs
(20 ischemic and 10 non-ischemic) >100 IMDs were performed without any negative consequence. The catheter system for electroporation is introduced into the femoral artery and steered retrograde across the aortic valve and secured to the myocardium in a region of interest. The heart is then paced through the catheter with 20 mA biphasic 10 msec capacitive discharge overdrive pacing at a rate selected to be 10 percent higher than the animals resting rate. This overdrive pacing prevents arrhythmias from the electroporation stimulation from arising. During the pacing interval, intramyocardial delivery is performed through the helix to the locally stimulated tissue. After delivery, pacing is terminated, the device is repositioned, and the procedure is repeated to cover the area of interest (individual injections encompass a local volume of approximately 1.5 cm3). Preliminary results with reporter gene studies in swine myocardium are underway.
Molecular Therapy, Vol 13, No 5, Abstract 774, May 2001.
