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Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping

^a Division of Cardiovascular Research, St. Elizabeth’s Medical Center, and Tufts University School of Medicine, Boston, Massachusetts, USA

View larger version (70K): [in a new window]   Figure 1 (A) The endocardial surface following dissection through the left lateral free wall following injections with methylene blue. Left ventricle with papillary muscles, left atrium and mitral valve apparatus are displayed. Lateral wall and septum are labeled. Methylene blue injection sites (arrows) are demonstrated at the apex, septum, and posterolateral wall. (B) Corresponding NOGATM map (left anterior oblique [LAO] projection) with injection sites indicated by red hexagons. LA = left arm; RA = right arm.

View larger version (61K): [in a new window]   Figure 2 Endocardial mapping and injection of normal male swine (RAO projection). NOGA maximum voltage and linear log shortening maps show injection sites into nonischemic myocardium. Note the coupling of normal mechanical function with normal electrical activity. Injections in this case were localized to the left ventricular apex. LA = left arm; RA = right arm.

View larger version (22K): [in a new window]   Figure 3 Quantitative beta-galactosidase assays of catheter-based single-site left ventricular (LV) injections in normal swine (pigs 3 to 8). Note the focal distribution of peak activity. A = anterior wall, L = lateral wall, P = posterior wall, S = septum. Numbers refer to the harvested tissue specimens, 1 being closest to the apex, and 4 being adjacent to the LV outflow tract and mitral valve ring.

View larger version (152K): [in a new window]   Figure 4 Fluoroscopic image (anteroposterior projection) of the injection catheter in the left ventricle angled toward the lateral wall. (Distal tip of injection catheter appears to point toward ameroid constrictor.)

View larger version (111K): [in a new window]   Figure 5 Catheter-based myocardial injections into ischemic swine left ventricle (LV). NOGATM electrical (maximum unipolar voltage) and mechanical (linear log shortening) maps of the swine LV are shown. Note area of ischemia in the lateral wall—normal electrical activity (blue/green) coupled with poor mechanical function (red). Images A and B represent anteroposterior projections demonstrating six injection sites (red hexagons) in an area of normal myocardial (apex) remote from the ischemic zone. Images C and D depict LAO projections of indicated injection sites in the ischemic lateral LV free wall. LA = left arm; RA = right arm.

View larger version (11K): [in a new window]   Figure 6 Quantitative beta-galactosidase assays of catheter-based single-site LV injections in swine models of chronic myocardial ischemia (pigs 9 and 10). Injections into myocardium remote from the ischemic zone are distinguished from injections made into the ischemic lateral wall. A = anterior wall, L = lateral wall, P = posterior wall, S = septum. Numbers refer to the harvested tissue specimens, 1 being closest to the apex, and 4 being adjacent to the LV outflow tract and mitral valve ring.