Could plasmid-mediated gene transfer into the myocardiurn be augmented by left ventricular guided laser myocardial injury?

Early studies have indicated no correlation between the amount of mechanica l injury and the level of myocardial gene expression following direct plasm id vector injection. Recently, however, evidence suggests that combined las er myocardial injury and plasmid-based gene delivery exert synergistic effe cts on gene expression and activity. The purpose of the study was to determ ine whether laser-induced myocardial injury followed by transendocardial ge ne transfer increases gene expression compared to gene transfer alone. We a ssessed the ability of a plasmid vector to express its transgene after inje ction into porcine ischemic myocardium with and without preceding laser myo cardial injury. Thirteen animals had transendocardial injections of the luc iferase reporter gene in a plamid vector using a catheter-based injection s ystem. Injections (0.5 mg per animal, 50 mug per injection site) were divid ed into 10 sites in the ischemic territory. Eight animals underwent transen docardial laser injury of the ischemic region (2 Joule per pulse x 10 sites ) prior to gene delivery. In five animals, gene injection sites were disper sed between laser channels, and in three animals laser and gene delivery we re applied in close proximity (< 5 mm) or at the same location. Luciferase activity was measured at 3 and 7 days. Luciferase expression in ischemic zo nes was markedly elevated at day 3 and 7, and similar whether animals were pretreated using laser injury followed by gene transfer compared to gene tr ansfer alone. Neither same-spot injection nor dispersed gene delivery were associated with augmented gene expression compared to gene transfer alone. Using the above-described catheter-based approach to combine localized lase r injury and injection of naked DNA into ischemic myocardium, laser injury did not augment gene expression above levels present with gene transfer alo ne. (C) 2001 Wiley-Liss, Inc.