Intracardiac echocardiographic guidance and monitoring during percutaneousendomyocardial gene injection in porcine heart

In an effort to develop a guiding and monitoring tool for transmyocardial g ene transfer, we have evaluated the feasibility of intracardiac echocardiog raphy (ICE) to guide percutaneous endomyocardial gene transfer (PEGT), and monitor complications, in a pig model. ICE (5.5-10 MHz), complemented by fl uoroscopy, was utilized to guide a needle injection into the heart in 19 no rmal pigs, Using this system, we injected Evans blue dye into eight pigs (g roup I), a mixture of pCK-CAT plasmid and India ink into seven pigs (group II), and pCK-LacZ plasmid into four pigs (group III), In all pigs, ICE cont ributed to the injection procedure by guiding the catheter to anatomically distinct sites, and by assisting stabilization of the catheter-endocardial contact. ICE predicted the injection sites correctly in 56 of 64 sites (87. 5%) in group I, and in 42 of 42 sites (100%) in group II. Leakage of inject ate into the left ventricular cavity could be detected by the microbubbles generated. The sites of injections appeared as foci of bright myocardial ec hodensity, which persisted until the end of the procedure. The procedures w ere not associated with significant morbidity or mortality. The expression of the chloramphenicol acetyltransferase (CAT) gene was identified in 40 si tes from 42 injections (95.2%) in group II. In group III, histology showed positive beta -galactosidase staining of myocytes limited around the needle track with low transfection efficiency (<1%). These results suggest that r eal-time ICE monitoring proves safe and useful during PEGT for guiding need le injection, monitoring leakage, ensuring delivery of injectate into the m yocardium, and instantly diagnosing cardiac complications, resulting in suc cessful gene transfer.