title: Incomplete retention after direct myocardial injection.
abstract: Direct intramyocardial injection may permit local delivery of protein and gene therapy agents for myocardial and coronary artery disease. Little is known about the immediate fate of materials administered via percutaneous endomyocardial catheters or via surgical epicardial injection. In this study, we use a novel method to evaluate the acute retention of agents injected directly into the myocardium, compare epicardial with the percutaneous endocardial and postmortem delivery, and evaluate the influence of injectate volume on myocardial retention. Fifteen 40-50 kg pigs underwent overlapping myocardial injections using a percutaneous endomyocardial catheter, an epicardial needle via an open chest, and epicardial needle postmortem. Multiple distinct 15 micro neutron-activated microsphere species were used as tracers. Two or three myocardial walls were injected in each animal using 3.5 mm, 27-28 gauge needles at varying injectate volumes. Animals were sacrificed immediately. Myocardial walls were divided and multiple microsphere species were quantified. In an additional study, nine 70 kg pigs underwent percutaneous endomyocardial injections with replication-deficient adenovirus encoding for the production of lac-Z. The injectate volume was varied, while the viral particle number remained constant. The animals were sacrificed 5 days after the percutaneous injections; the heart, liver, and spleen were collected for beta-galactosidase activity. Endomyocardial injection was associated with 43% +/- 15% microsphere retention, compared with 15% +/- 21% (P < 0.01) retention of open chest epicardial injection and 89% +/- 60% (P < 0.01) for postmortem injection. Reducing the injectate volume from 100 to 10 microL improved microsphere retention (P = 0.01). There was a trend toward improved viral transfection associated with smaller injection volumes. Despite direct intramyocardial administration, a significant fraction of injectate is not retained locally. Catheter-based needle endomyocardial injection is associated with equivalent or superior injectate retention compared with open chest epicardial injection. Proportionately, more injectate may be retained at lower volumes. Loss may involve a combination of channel leakage, venous, and lymphatic return.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Grossman
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Han
authors.forename: Maria
authors.initials: M
authors.lastname: Palasis
authors.forename: James J
authors.initials: JJ
authors.lastname: Barry
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lederman
mesh_terms: D000256:Adenoviridae; D000818:Animals; D006328:Cardiac Catheterization / Q000295:instrumentation / Q000379:methods; D016503:Drug Delivery Systems; D005471:Fluoroscopy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007267:Injections / Q000379:methods*; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism*; D009339:Needles; D013552:Swine; D014162:Transfection / Q000379:methods; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase