title: Evaluation of a novel ECG lead placement method in telemetered freely moving cynomolgus monkeys: assessment of an intravascular biopotential lead.
abstract: BACKGROUND
  ECG is considered as a critical biomarker of cardiac safety pharmacology. ECG signal quality is essential for accurate interval quantification and automated arrhythmia detection.
  
  
  METHODS
  We evaluated ECG signal quality over a 6 month period from 15 cynomolgus monkeys with radiotelemetry transmitters using biopotential leads where the negative lead was inserted in the jugular vein and advanced to the superior vena cava (intravascular lead) and the positive lead was placed on the diaphragm at the apex of the heart (diaphragmatic lead). Signal noise and signal-to-noise ratio from this implantation methodology were compared with signals obtained from animals with subcutaneous ECG lead. Macroscopic pathology and histopathology associated with the intravascular lead were evaluated at 6 months post-implantation in six monkeys.
  
  
  RESULTS
  The ECG morphology obtained with the intravascular/diaphragmatic lead placement was comparable to conventional subcutaneous ECG (emulating Lead II) but presented higher amplitudes (P-wave +50.0%; R-wave +30.0%). Signal noise showed a circadian cycle of changes in magnitude for subcutaneous ECG leads that was not observed with this method. The intravascular/diaphragmatic lead placement presented a higher signal-to-noise ratio than subcutaneous ECG leads. No macroscopic abnormality was observed to be associated with the intravascular lead. Mild thickening of the intima/subintima with mild intimal proliferation of the cranial vena cava surrounding the intravascular lead were noted at histopathological examination.
  
  
  CONCLUSIONS
  The intravascular/diaphragmatic ECG lead placement in cynomolgus monkeys provided reduced signal noise and elevated P-QRS-T amplitudes. The intravascular lead was well tolerated and appeared suitable for chronically instrumented cardiovascular safety pharmacology studies. Further assessments would be warranted to evaluate the potential of this methodology in other species.
authors.affiliation: LAB Research Inc., 445 Armand Frappier, Laval, Quebec, Canada. authiers@labresearch.com
authors.forename: S
authors.initials: S
authors.lastname: Authier
authors.forename: L B
authors.initials: LB
authors.lastname: Moon
authors.forename: M
authors.initials: M
authors.lastname: Stonerook
authors.forename: S
authors.initials: S
authors.lastname: Fournier
authors.forename: J
authors.initials: J
authors.lastname: Gervais
authors.forename: S
authors.initials: S
authors.lastname: Maghezzi
authors.forename: E
authors.initials: E
authors.lastname: Troncy
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004562:Electrocardiography / Q000295:instrumentation / Q000379:methods*; D004567:Electrodes, Implanted; D005260:Female; D008252:Macaca fascicularis; D013686:Telemetry / Q000379:methods*; D013997:Time Factors; D014683:Vena Cava, Superior