Circulation, Vol 85, 1582-1593, Copyright © 1992 by American Heart Association
B Avitall, J Hare, G Zander, C Bockoff, P Tchou, M Jazayeri and M Akhtar
BACKGROUND. Antiarrhythmic drugs often fail to achieve therapeutic effects
without toxic systemic levels. Direct transport of drugs into the
myocardium may circumvent this problem and may also provide new insights
into antiarrhythmic drug effect on arrhythmogenic tissues. In a canine
model, procainamide (PA) was delivered iontophoretically using pulsed
current synchronized with the ventricular depolarization via an implantable
defibrillator patch electrode that was modified to contain a 3.6-ml
chamber. Myocardial tissue concentrations of PA were evaluated in 7-day
myocardial infarcts (n = 16) that were exposed to 10 minutes of
iontophoretic PA delivery and compared with passive diffusion (n = 5) and
intravenous (n = 16) PA. These dogs were followed for 3 hours. The
infarcted tissue PA levels were compared with normal myocardium. Coronary
and systemic blood levels of PA, effective refractory period (ERP),
diastolic threshold, and efficacy of ventricular tachycardia (VT)
suppression were evaluated throughout the follow-up period. METHODS AND
RESULTS. Three hours after 10 minutes of iontophoretic, passive, and
intravenous PA, the epicardial layer concentration in the center of the
infarcted zone was 840 +/- 853 micrograms/g, 93 +/- 90 micrograms/g, and 15
+/- 8 micrograms/g of tissue, respectively. In the endocardial layer, the
PA concentrations with iontophoresis were 38 +/- 57 micrograms/g and were
significantly higher than those achieved with either passive diffusion 38
+/- (4 +/- 2 micrograms/g) or with intravenous delivery (11 +/- 5
micrograms/g) (p less than 0.05). Epicardial tissue PA concentrations 3
hours after iontophoresis, passive diffusion, and intravenous PA in the
normally perfused tissues were 14 +/- 13 micrograms/g, 3 +/- 2
micrograms/g, and 16 +/- 8 micrograms/g of PA, respectively. Venous blood
levels were 2 +/- 3 micrograms/ml 3 hours after iontophoresis, 1 +/- 1
microgram/ml 3 hours after passive PA delivery, and 11 +/- 7 micrograms/ml
with intravenous administration (p less than 0.05 intravenous versus
passive and iontophoresis). Iontophoretic delivery of PA resulted in 22 +/-
29 msec ERP prolongation intramurally in the infarcted zone with no
significant normal tissue ERP prolongation. Passive delivery of PA produced
no significant changes in ERP. After intravenous infusion, the ERP in the
infarcted zone increased by 35 +/- 29 msec and 13 +/- 12 msec in the normal
tissue. Sustained monomorphic VT was induced in 20 animals. In one of these
animals, only nonsustained VT could be induced at baseline; however, after
intravenous PA, VT could be induced and remained inducible throughout the
3-hour follow-up period. In the iontophoretic delivery group, PA suppressed
VT in all of the animals, with termination time ranging from 20 seconds to
7 minutes. In three cases, sustained monomorphic VT could be reinduced, two
after 60 minutes and one after 120 minutes. However, in seven dogs, VT
could not be induced during the 3-hour follow-up period. None of the dogs
in which PA was delivered iontophoretically into the infarcted myocardium
developed VT that was not induced before delivery of the drug. Intravenous
PA administration resulted in VT suppression in one of 10 dogs. In two
dogs, VT could not be induced before intravenous infusion of PA. However,
after intravenous PA, VT could be induced. Immunohistochemical mapping of
the PA within the infarcted tissue revealed transmural PA distribution.
CONCLUSIONS. These data show that 1) the delivery of high transmural
concentrations of PA directly into infarcted myocardium is both feasible
and effective...
ARTICLES
Iontophoretic transmyocardial drug delivery. A novel approach to antiarrhythmic drug therapy
Cardiac Electrophysiology Laboratory, University of Wisconsin Milwaukee Clinical Campus, Sinai Samaritan Medical Center 53233.
This article has been cited by other articles:
 |
|
 |
|
  P. J. Wang Rate Control: Is Local Better? Circulation, May 23, 2006; 113(20): 2374 - 2376. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Waxman, R. Moreno, K. A. Rowe, and R. L. Verrier Persistent primary coronary dilation induced by transatrial delivery of nitroglycerin into the pericardial space: a novel approach for local cardiac drug delivery J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2073 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Verrier, S. Waxman, E. G. Lovett, and R. Moreno Transatrial Access to the Normal Pericardial Space : A Novel Approach for Diagnostic Sampling, Pericardiocentesis, and Therapeutic Interventions Circulation, November 24, 1998; 98(21): 2331 - 2333. [Abstract] [Full Text] [PDF]
|
|