UCLA Cardiac Arrhythmia Center, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, and Department of Cardiac Anesthesia, University of California, Los Angeles, CA.
Circ Arrhythm Electrophysiol. 2013 Aug;6(4):776-83. doi: 10.1161/CIRCEP.113.000448. Epub 2013 Jul 19.
Radiofrequency ablation for ventricular tachycardia is an established therapy. Use of chemical agents for scar homogenization represents an alternative approach. The purpose of this study was to characterize the efficacy of collagenase (CLG) application on epicardial ventricular scar homogenization.
Myocardial infarcts were created in Yorkshire pigs (n=6) by intracoronary microsphere injection. After 46.6±4.3 days, CLG type 2, type 4, and purified CLG were applied in vitro (n=1) to myocardial tissue blocks containing normal myocardium, border zone, and dense scar. Histopathologic studies were performed to identify the optimal CLG subtype. In vivo high-density electroanatomic mapping of the epicardium was also performed, and border zone and dense scar surface area and late potentials were quantified before and after CLG-4 application (n=5). Of the CLG subtypes tested in vitro, CLG-4 provided the best scar modification and least damage to normal myocardium. During in vivo testing, CLG-4 application decreased border zone area (21.3±14.3 to 17.1±11.1 mm(2), P=0.043) and increased dense scar area (9.1±10.3 to 22.0±20.6 mm(2), P=0.043). The total scar area before and after CLG application was 30.4±23.4 and 39.2±29.5 mm(2), respectively (P=0.08). Late potentials were reduced by CLG-4 application (28.8±21.8 to 13.8±13.1, P=0.043). During CLG-4 application (50.0±15.5 minutes), systolic blood pressure and heart rate were not significantly changed (68.0±7.7 versus 61.8±5.3 mmHg, P=0.08; 77.4±7.3 versus 78.8±6.0 beats per minute, P=0.50, respectively).
Ventricular epicardial scar homogenization by CLG-4 application is feasible and effective. This represents the first report on bioenzymatic ablation of arrhythmogenic tissue as an alternative strategy for lesion formation.
射频消融术是治疗室性心动过速的一种已确立的疗法。使用化学剂进行瘢痕匀化是另一种方法。本研究的目的是描述胶原酶（CLG）在心脏外膜心室瘢痕匀化中的疗效。
通过冠状动脉内微球注射，在约克郡猪（n=6）中创建心肌梗死。在 46.6±4.3 天后，将 CLG 2 型、4 型和纯化 CLG 应用于含有正常心肌、边缘区和致密瘢痕的心肌组织块中（n=1）。进行组织病理学研究以确定最佳 CLG 亚型。还对心脏外膜进行了高密度电解剖标测，并在 CLG-4 应用前后（n=5）量化了边界区和致密瘢痕的表面积和晚期电位。在体外测试的 CLG 亚型中，CLG-4 可提供最佳的瘢痕修饰效果，对正常心肌的损伤最小。在体内试验中，CLG-4 应用减少了边缘区面积（21.3±14.3 至 17.1±11.1mm²，P=0.043），增加了致密瘢痕面积（9.1±10.3 至 22.0±20.6mm²，P=0.043）。CLG 应用前后的总瘢痕面积分别为 30.4±23.4 和 39.2±29.5mm²（P=0.08）。CLG-4 应用降低了晚期电位（28.8±21.8 至 13.8±13.1，P=0.043）。在 CLG-4 应用期间（50.0±15.5 分钟），收缩压和心率没有明显变化（68.0±7.7 与 61.8±5.3mmHg，P=0.08；77.4±7.3 与 78.8±6.0 次/分钟，P=0.50）。
通过 CLG-4 应用进行心室外膜瘢痕匀化是可行且有效的。这是首例关于生物酶消融致心律失常组织作为病变形成替代策略的报告。
