title: Benefits of standardizing the treatment of arrhythmias in the sheep (Ovis aries) model of chronic heart failure after myocardial infarction.
abstract: Large animal models of heart failure are essential in preclinical device testing. In sheep, catheter-based coil embolization of the left anterior descending and diagonal artery provides a minimally invasive and reproducible model of myocardial infarction (MI). Although widely used, this model has historically been plagued with a 30% mortality rate, both in the literature and in our own experience. Our study endeavored to decrease the mortality rate by targeting the most common cause of death, intractable arrhythmias, during creation of the ovine MI model. To this end, we evaluated 2 methods of managing perioperative antiarrhythmic therapy and cardiopulmonary resuscitation during model creation. The first group of sheep was managed at the discretion of the individual operator, whereas the second group was treated according to a standardized protocol that included mandatory pretreatment with amiodarone. Sheep experiencing life-threatening arrhythmias, most commonly ventricular fibrillation, were either resuscitated according to operator-driven instructions or the standardized protocol. By comparing these 2 treatment groups, we have shown that using a standardized protocol is advantageous in reducing mortality associated with the ovine MI model. Since implementing the standardized protocol, our laboratory has lowered the expected mortality rate to 10% during catheter-based induction of ovine MI and has greatly reduced the number of animals required for study needs. In addition, the standardized protocol has proven beneficial in training new staff members. By implementing this standardized method of model management, the outcomes of model creation have been optimized.
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, New York, USA. adardenne@crf.org
authors.forename: Adrienne
authors.initials: A
authors.lastname: Dardenne
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez
authors.forename: Alyssa
authors.initials: A
authors.lastname: Wagner
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Milewski
authors.forename: Diane R
authors.initials: DR
authors.lastname: Ordanes
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Mount
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cheng
authors.forename: Geng-Hua
authors.initials: GH
authors.lastname: Yi
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Conditt
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: William P
authors.initials: WP
authors.lastname: Feeney
mesh_terms: D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D057785:Catheters; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D059035:Perioperative Period / Q000401:mortality; D034561:Sheep, Domestic; D016277:Ventricular Function, Left
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone