Dd. Hodgkin et al., ELECTROPHYSIOLOGIC CHARACTERISTICS OF A PULSED IONTOPHORETIC DRUG-DELIVERY SYSTEM IN CORONARY-ARTERIES, Journal of cardiovascular pharmacology, 29(1), 1997, pp. 39-44
This study evaluated the electrophysiologic effects of a pulsed iontop
horetic drug-delivery system when used in the coronary arteries. Preve
ntion of acute thrombosis and restenosis after intravascular procedure
s may be enhanced by high concentrations of therapeutic agents within
the vessel wall. A new intravascular drug-delivery system uses iontoph
oresis to maximize local tissue concentrations of drug. However, the e
lectrophysiologic effects of such a system in coronary arteries are un
known. An iontophoretic membrane balloon-tipped catheter was placed fl
uoroscopically in the mid left anterior descending coronary artery of
10 anesthetized dogs. Strength-duration curves and effective refractor
y period (ERP) were initially determined. Threshold for capture was as
sessed at pulse widths of 0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occu
rred 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 [prem
ature beats >10/min, supraventricular tachycardia (SVT), ventricular t
achycardia (VT), ventricular fibrillation (VF)], by using sequential s
teps of 1, 5, 10, 15, and 20 mA. Highest average outputs achieved with
out an arrhythmia were 14.1+/-2.5 and 4.9+/-2.0 mA at 50 and 75% of ER
P, respectively (p <0.05). High-grade arrhythmias (pulseless VT or VF)
occurred in three of four animals studied before use of a frequency l
imiter, 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 fiel
d with a response-frequency limiter can be safely used within the cani
ne coronary arterial system at 50% of ERP with moderate outputs (5-10
mA). Increasing the stimulus duration to 75% of ERP increases arrhythm
ogenesis but is tolerated at lower output levels (<5 mA).