title: Intravenous solid tip ECG lead placement in telemetry implanted dogs: Part 2: High quality telemetry signals yield high sensitivity to drug-induced changes.
abstract: BACKGROUND
  Dogs are commonly used in cardiovascular drug safety assessment, and implanted telemetry models include subcutaneous or epicardial electrocardiogram (ECG) electrode placements. The purpose of this study was to determine the sensitivity of a canine telemetry model with intravenous ECG lead placement: the negative ECG lead (solid tip) inserted into the jugular vein and the positive lead sutured to the diaphragm. Reference drugs were administered to test the sensitivity to drug-induced changes.
  
  
  METHODS
  Twenty-four dogs were implanted with PCT or PCTP transmitters [Data Sciences International (DSI)]. Three reference drugs were administered: sotalol to eight PCT and milrinone to eight PCTP transmitter-implanted dogs. Twenty-four dogs received moxifloxacin (12 dogs/transmitter type). Telemetry data were collected for 25h and analyzed using double Latin squares for sotalol and milrinone data or a 4×4 or 3×6 parallel design for moxifloxacin data. Evaluated parameters were PR, QT, corrected QT (QTc), QRS, heart rate, left ventricular function, and hemodynamic data. Various correction factors for QTc interval were tested. Retrospective power analysis was performed to detect minimal absolute changes comparing a single to a double Latin square or the two parallel designs.
  
  
  RESULTS
  Expected changes on ECG and hemodynamic parameters were observed after administration of all reference drugs. The individual animal corrected QT (QTci) interval provided the optimal correction factor. Retrospective power analysis confirmed detection of smaller differences in double versus single Latin squares. Minimal detectable differences were smaller in both Latin squares compared to parallel designs, with smaller detectable differences in a 3×6 compared to a 4×4 parallel design.
  
  
  CONCLUSIONS
  The solid tip intravenous ECG lead configuration in dogs is a viable radiotelemetry model to detect drug-induced changes with high sensitivity. This model yields comparable signal quality and represents a refinement over epicardial ECG leads and allows for possible reduction in the number of animals if study design and size are selected based on needed assay sensitivity.
authors: Covance Laboratories Inc., 3301 Kinsman Boulevard, Madison, WI 53704,USA. andrea.mitchell@covance.com
authors: Andrea Z
authors: AZ
authors: Mitchell
authors: Andrew J
authors: AJ
authors: Bills
authors: Gary T
authors: GT
authors: Wittwer
authors: C Michael
authors: CM
authors: Foley
authors: John J
authors: JJ
authors: Kremer
authors: Hepei
authors: H
authors: Chen
authors: Mark A
authors: MA
authors: Osinski
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000633:toxicity; D004285:Dogs; D004562:Electrocardiography / Q000379:methods*; D004567:Electrodes, Implanted; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007601:Jugular Veins; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D020105:Milrinone / Q000633:toxicity; D000077266:Moxifloxacin; D011804:Quinolines / Q000633:toxicity; D012680:Sensitivity and Specificity; D013015:Sotalol / Q000633:toxicity; D013686:Telemetry / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D013015:Sotalol; D020105:Milrinone; D000077266:Moxifloxacin
keywords: Cardiovascular; Dogs; ECG; Preclinical; Surgical methods; Telemetry