Use of a novel endoscopic catheter for direct visualization and ablation in an ovine model of chronic myocardial infarction.

BACKGROUND: Defining the arrhythmogenic substrate is essential for successful ablation of scar-related ventricular tachycardia. The visual characteristics of endocardial ischemic scar have not been described in vivo. The goal of this study was (1) to quantify the visual characteristics of normal tissue, scar border zone, and dense scar in vivo with the use of a novel endoscopic catheter that allows direct endocardial visualization and (2) to correlate visual attributes of myocardial scar with bipolar voltage. METHODS AND RESULTS: Percutaneous transient balloon occlusion (150 minutes) of the mid left anterior descending coronary artery was performed in an ovine model. Animals survived for 41.5±0.7 days. Detailed bipolar voltage maps of the left ventricle were acquired with the use of NavX. Video snapshots of the endocardium were acquired at sites distributed throughout the left ventricle. Visual tissue characteristics of normal (>1.5 mV), border (0.5-1.5 mV), and dense scar (<0.5 mV) were quantified with the use of image processing. Radiofrequency lesions (10-20 W, 30 seconds) were delivered under direct visualization. Mean white-threshold pixel area was lowest in normal tissue (189 969±41 478 pixels(2)), intermediate in scar border zone (255 979±36 016 pixels(2)), and highest in dense scar (324 452±30 152 pixels(2); P<0.0001 for all pairwise comparisons). Tissue whiteness, characteristic of scar, was inversely correlated with bipolar voltage (P<0.0001). During radiofrequency lesions, there was a significant increase in white-thresholded pixel area of the visual field after ablation (average increase, 85 381±52 618 pixels(2); P<0.001). CONCLUSIONS: Visual characteristics of chronic infarct scar in vivo observed with the use of a novel endoscopic catheter correlate with bipolar electrogram voltage. Irrigated radiofrequency lesions in normal endocardial tissue and postinfarction zone can be visualized and quantified with the use of image processing. This technology shows promise for visually based delivery of radiofrequency lesions for the treatment of scar-based ventricular tachycardia.

In vivo evaluation of virtual electrode mapping and ablation utilizing a direct endocardial visualization ablation catheter.

BACKGROUND: Radiofrequency (RF) ablation utilizing direct endocardial visualization (DEV) requires a "virtual electrode" to deliver RF energy while preserving visualization. This study aimed to: (1) examine the virtual electrode RF ablation efficacy; (2) determine the optimal power and duration settings; and (3) evaluate the utility of virtual electrode unipolar electrograms. METHODS AND RESULTS: The DEV catheter lesions were compared to lesions formed using a 3.5 mm open irrigated tip catheter within the right atria of 12 sheep. Generator power settings for DEV were titrated from 12W, 14W and 16W for 20, 30 and 40 seconds duration with 25 mL/min saline irrigation. Standard irrigated tip catheter settings of 30W, 50°C for 30 seconds and 30 mL/min were used. The DEV lesions were significantly greater in surface area and both major and minor axes compared to irrigated tip lesions (surface area 19.43 ± 9.09 vs 10.88 ± 4.72 mm, P<0.01) with no difference in transmurality (93/94 vs 46/47) or depth (1.86 ± 0.75 vs 1.85 ± 0.57 mm). Absolute electrogram amplitude reduction was greater for DEV lesions (1.89 ± 1.31 vs 1.49 ± 0.78 mV, P = 0.04), but no difference in percentage reduction. Pre-ablation pacing thresholds were not different between DEV (0.79 ± 0.36 mA) and irrigated tip (0.73 ± 0.25 mA) lesions. There were no complications noted during ablation with either catheter. CONCLUSIONS: Virtual electrode ablation consistently created wider lesions at lower power compared to irrigated tip ablation. Virtual electrode electrograms showed a comparable pacing and sensing efficacy in detecting local myocardial electrophysiological changes.

Oligocarbamate molecular transporters: design, synthesis, and biological evaluation of a new class of transporters for drug delivery.

Molecular transporters have the ability to deliver drugs and probe molecules into cells and tissues irrespective of their physical properties. We now report the design, synthesis, and biological evaluation of a new family of molecular transporters, guanidinylated oligocarbamates that enable exceptionally efficient uptake into cells and tissues. The synthesis features a solid-phase stepwise oligomerization to obtain the oligocarbamates and a single step perguanidinylation for the facile introduction of up to nine guanidinium groups. The oligocarbamate 9-mer is found to be among the most efficient transporters known, entering cells faster than even d-Arg9 and HIV-1 Tat49-57. Significantly, this new family of transporters also enables uptake into the formidable skin barrier of a probe molecule that by itself does not penetrate skin.

Arginine-rich molecular transporters for drug delivery: role of backbone spacing in cellular uptake.

Short oligomers of arginine, either alone or when conjugated to therapeutic agents or large biopolymers, have been shown to cross readily a variety of biological barriers (e.g., lipid bilayers and epithelial tissue). Molecular modeling suggests that only a subset of the side chain guanidinium groups of these transporters might be required for transport involving contact with a common surface such as a plasma membrane or cell surface receptor. To evaluate this hypothesis, a series of decamers were prepared that incorporated seven arginines and three nonarginine residues. Several of these mixed decamers were comparable to the all arginine decamer in their ability to enter cells. More significantly, these decamers containing seven arginines performed almost without exception better than heptaarginine itself, suggesting that spacing between residues is also important for transport. The influence of spacing was more fully evaluated with a library of oligomers incorporating seven arginines separated by one or more nonconsecutive, non-alpha-amino acids. This study led to the identification of a new series of highly efficient molecular transporters.