title: Validation and utility of the PhysioTel™ Digital M11 telemetry implant for cardiovascular data evaluation in cynomolgus monkeys and Beagle dogs.
abstract: BACKGROUND
  The cardiovascular liability of candidate compounds can be evaluated by a number of methods including implanted telemetry, jacketed telemetry and surface lead electrocardiogram (ECG). The utility of the new PhysioTel™ Digital M11 cardiovascular telemetry implant was evaluated in monkeys and dogs.
  
  
  METHODS
  Eight monkeys and dogs (4 males and 4 females per species) were implanted with the M11 device utilizing a femoral blood pressure catheter and periosteal ECG leads. The signal quality of the ECGs was determined as a percentage of software-matched waveforms and as a percentage of signal loss during the recording periods. To investigate sensitivity for detecting changes in QT/QTc and HR/BP, moxifloxacin and doxazosin were administered to monkeys and dogs implanted with the M11 device. Additionally, histopathological evaluation of the implant site was completed.
  
  
  RESULTS
  For both monkey and dog, the percentage of recognizable waveforms was high (65% and 85%, respectively), while the average amount of signal loss was low (1% and 3%, respectively), indicating that the M11 implants delivered data of sufficient quality. In monkeys, moxifloxacin (90mg/kg) induced QT and QTc prolongation up to 22 and 12ms, respectively, while at 30mg/kg in dogs, the maximal increases in QT and QTc were 13 and 16ms, respectively. Doxazosin (1.5 and 1.0mg/kg) produced HR increases up to 35 and 29bpm with decreases in blood pressure up to -14 and -26mmHg in monkeys and dogs, respectively. The histopathological impact of the implant, catheter and biopotential leads was limited to expected minor local inflammatory changes as assessed at necropsy and with microscopic examination.
  
  
  CONCLUSIONS
  Based upon the results of this study, the PhysioTel™ Digital M11 is a suitable technology for assessing cardiovascular parameters in monkeys and dogs, and because of the size and limited invasiveness of the implant, is well positioned for use on toxicology studies.
authors: Pfizer, Eastern Point Road, Groton, CT, USA. Electronic address: Jason.s.cordes@pfizer.com.
authors: Jason S
authors: JS
authors: Cordes
authors: Pfizer, 10777 Science Center Drive, San Diego, CA, USA.
authors: Jonathan R
authors: JR
authors: Heyen
authors: Pfizer, Eastern Point Road, Groton, CT, USA.
authors: Marlo L
authors: ML
authors: Volberg
authors: Research Surgery and Veterinary Consulting, San Francisco Bay Area, CA, USA.
authors: Nancy
authors: N
authors: Poy
authors: Pfizer, Eastern Point Road, Groton, CT, USA.
authors: Steven
authors: S
authors: Kreuser
authors: Pfizer, Eastern Point Road, Groton, CT, USA.
authors: Ahmed M
authors: AM
authors: Shoieb
authors: Pfizer, Eastern Point Road, Groton, CT, USA.
authors: Jill
authors: J
authors: Steidl-Nichols
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D017292:Doxazosin / Q000494:pharmacology; D004562:Electrocardiography / Q000379:methods; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008133:Long QT Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D008252:Macaca fascicularis; D008297:Male; D000077266:Moxifloxacin; D013686:Telemetry / Q000379:methods*
chemical_list: D024841:Fluoroquinolones; D017292:Doxazosin; D000077266:Moxifloxacin
keywords: Cardiovascular; Doxazosin; JET; M11; Moxifloxacin; PhysioTel™ Digital; QTc prolongation; Safety pharmacology; Telemetry