title: Effects of telemetric epicardial leads and ventricular catheters on arrhythmia incidence in cynomolgus monkeys.
abstract: BACKGROUND
  Utilization of implantable bio-telemetry devices represents a common approach to contemporary cardiovascular safety assessment. Depending on the specific needs of the study design, and corresponding surgical methodologies employed, application of telemetry devices may have more or less liability to interact with ongoing physiology. The potential for intrathoracic procedures (epicardial/intracardiac ECG lead arrangements, left ventricular catheterization) to influence baseline cardiovascular function, and particularly arrhythmia status is currently an important topic of consideration.
  
  
  METHODS
  Two experiments were performed to assess the post-surgical incidence of ventricular arrhythmias in cynomolgus monkeys instrumented with telemetry devices with 1) left ventricular pressure (LVP) transducers and epicardial lead array (N=67), and 2) epicardial lead array without LVP catheter placement (N=55). A third experiment (N=18) was performed to prospectively, and definitively, investigate the effect of chronic left ventricular catheterization on the observed incidences of arrhythmias by means of multiple (pre- and post-surgery) electrocardiographic evaluations conducted on ~24h of data per interval assessed up to ~12months post-implantation.
  
  
  RESULTS
  The diversity and number of ventricular rhythm variants was considerably greater in animals instrumented with left ventricular catheters (62/67; 93%) compared to animals instrumented with epicardial leads only (21/55; 38.2%), and surgically naïve animals (9/18; 50%). Prior to surgery, the average frequency of all definitively characterized arrhythmias among experimentally naïve animals was 0.19/h; following surgical implantation of the telemetry device with epicardial leads and ventricular pressure catheter, the overall frequency of arrhythmia increased approximately 40-fold, to 7.19/h.
  
  
  CONCLUSIONS
  Similar to prior investigations in canines, the present results confirm an increased incidence in the rate and variety of ventricular arrhythmias in cynomolgus monkeys when instrumented with telemetry devices equipped with LVP catheters. Instrumentation with epicardial leads was not associated with an increase in arrhythmias above that expected as a function of normal biological variation in experimentally naïve animals of this species.
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA. Electronic address: david.holdsworth@mpiresearch.com.
authors.forename: David L
authors.initials: DL
authors.lastname: Holdsworth
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: O'Donohue
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Yoder
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: Janelle E
authors.initials: JE
authors.lastname: Gesaman
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Dalton
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Gauvin
authors.affiliation: VetMed Consultants, Inc., Comparative Cardiology Division, 1704-B Llano St., Suite 279, Santa Fe, NM 87505, USA.
authors.forename: Larry P
authors.initials: LP
authors.lastname: Tilley
authors.affiliation: VetMed Consultants, Inc., Comparative Cardiology Division, 4 Clematis Rd, Lexington, MA 02421-7117, USA.
authors.forename: Francis W K
authors.initials: FW
authors.lastname: Smith
authors.affiliation: Safety Pharmacology, MPI Research, Inc., 54943 North Main St., Mattawan, MI 49071-9399, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Baird
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D016477:Artifacts; D057785:Catheters / Q000009:adverse effects*; D004562:Electrocardiography; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D013686:Telemetry / Q000009:adverse effects* / Q000295:instrumentation*; D017725:Ventricular Pressure
keywords: Arrhythmia; Cynomolgus; ECG; Epicardial lead; Monkey; Telemetry; Ventricular catheter; Ventricular pressure