title: Electrophysiologic characteristics of a pulsed iontophoretic drug-delivery system in coronary arteries.
abstract: This study evaluated the electrophysiologic effects of a pulsed iontophoretic drug-delivery system when used in the coronary arteries. Prevention of acute thrombosis and restenosis after intravascular procedures may be enhanced by high concentrations of therapeutic agents within the vessel wall. A new intravascular drug-delivery system uses iontophoresis to maximize local tissue concentrations of drug. However, the electrophysiologic effects of such a system in coronary arteries are unknown. An iontophoretic membrane balloon-tipped catheter was placed fluoroscopically in the mid left anterior descending coronary artery of 10 anesthetized dogs. Strength-duration curves and effective refractory period (ERP) were initially determined. Threshold for capture was assessed at pulse widths of 0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occurred at 4.9 +/- 0.9, 3.4 +/- 0.5, 2.6 +/- 0.5, 1.6 +/- 0.2, and 1.2 +/- 0.2 mA, respectively. The ERP was 169 +/- 6 ms (4.0-ms pulses at twice threshold). Then square-wave pulses for iontophoresis were R-wave synchronized and delivered at 50 and 75% of the ERP with the balloon inflated to 1 atm. Output was increased until significant arrhythmias occurred [premature beats > 10/min, supraventricular tachycardia (SVT), ventricular tachycardia (VT), ventricular fibrillation (VF)], by using sequential steps of 1, 5, 10, 15, and 20 mA. Highest average outputs achieved without an arrhythmia were 14.1 +/- 2.5 and 4.9 +/- 2.0 mA at 50 and 75% of ERP, respectively (p < 0.05). High-grade arrhythmias (pulseless VT or VF) occurred in three of four animals studied before use of a frequency limiter, which allowed current delivery only at intervals > 400 ms (thus inhibiting current activation during premature beats). No further VT or VF occurred in the remaining six animals, except for one episode of nonsustained VT (11 beats). An R-wave synchronized iontophoretic field with a response-frequency limiter can be safely used within the canine coronary arterial system at 50% of ERP with moderate outputs (5-10 mA). Increasing the stimulus duration to 75% of ERP increases arrhythmogenesis but is tolerated at lower output levels (< 5 mA).
authors.affiliation: Department of Cardiology, VA Medical Center, Minneapolis, MN 55417, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Hodgkin
authors.forename: G L
authors.initials: GL
authors.lastname: Pierpont
authors.forename: K R
authors.initials: KR
authors.lastname: Hildebrand
authors.forename: C C
authors.initials: CC
authors.lastname: Gornick
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D016503:Drug Delivery Systems / Q000009:adverse effects* / Q000379:methods; D004594:Electrophysiology; D005260:Female; D007478:Iontophoresis / Q000009:adverse effects* / Q000379:methods; D008297:Male; D017180:Tachycardia, Ventricular / Q000209:etiology*; D014693:Ventricular Fibrillation / Q000209:etiology*