title: Electrical homogenization of ventricular scar by application of collagenase: a novel strategy for arrhythmia therapy.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Daigo
authors.initials: D
authors.lastname: Yagishita
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.forename: Marmar
authors.initials: M
authors.lastname: Vaseghi
authors.forename: Ali
authors.initials: A
authors.lastname: Nsair
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Roderick
authors.initials: R
authors.lastname: Tung
authors.forename: Aman
authors.initials: A
authors.lastname: Mahajan
authors.forename: Kalyanam
authors.initials: K
authors.lastname: Shivkumar
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D000200:Action Potentials; D000818:Animals; D002921:Cicatrix / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000008:administration & dosage*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D056149:Epicardial Mapping; D005240:Feasibility Studies; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D017180:Tachycardia, Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D003094:Collagen; D017364:Collagenases
keywords: bioenzymatic ablation; collagenase; radiofrequency; scar homogenization; ventricular tachycardia