Evaluation of electrocardiograms recorded in cynomolgus monkeys with short- and long-term intracardiac lead implantations.
BACKGROUND
minimally invasive placement of intracardiac (IC) ECG leads in monkeys has greatly improved signal quality and the ability to interpret these ECGs. However, information on characteristics of the ECGs recorded using the IC lead is not available in the literature. There are concerns about the potential impact of IC lead placement on the ECG waveform and cardiac function as a result of potential irritation or trauma resulting from the placement and/or long term residence of the IC lead. The purposes of this study were to characterize IC ECG morphology, to obtain information on the recovery processes after IC ECG lead implantation, and to evaluate the IC ECG model application to safety pharmacology studies.


METHODS
the telemetry transmitter, arterial blood pressure catheter and IC ECG lead were implanted in 40 cynomolgus monkeys, two of which were also implanted with subcutaneous (SC) ECG leads. The data of IC ECG, heart rate (HR) and mean arterial blood pressure (MABP) were collected telemetrically for a period of 1-12 months after implantation, and measured using computer softwares.


RESULTS
the IC ECG waveforms varied greatly from those of SC ECG. There was no clearly identifiable S-T segment, and T waves were biphasic in the majority of IC ECGs. The morphology of IC ECG was diversified among animals, progressively changed in the first 2 weeks post-surgery and stabilized approximately 3 weeks post-surgery. MABP and HR were elevated after implant surgery, but recovered to the levels comparable to those of SC in approximately 1 and 4 weeks, respectively. The IC ECG values obtained during week 8 to 10 (HR=134+/-25 bpm, PR interval=87+/-13 ms, QRS interval=40+/-7 ms, and QT interval=246+/-30 ms, QTcF=318+/-28 ms) were comparable to those from SC ECG.


CONCLUSIONS
the IC ECG provides a clear ECG signal with values comparable to, and waveforms different from, SC recordings. The complicated surgical procedure with long substantial recovery time, high incidence of IC lead malfunction, and high costs for IC leads may limit application of the IC ECG model in safety pharmacology studies.
Yao
Jian-An
JA
BioResources, Wyeth Research, Pearl River, New York 10965, USA. yaoj2@wyeth.com
Feldman
Hal S
HS
Illenberger
Arthur
A
Littell
Todd
T
Schnee
Laura
L
Yates
David
D
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004562:Electrocardiography / Q000295:instrumentation* / Q000379:methods*; D004582:Electronics, Medical; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D008252:Macaca fascicularis; D008297:Male; D012984:Software; D013686:Telemetry / Q000379:methods; D013997:Time Factors