Evaluation of a novel ECG lead placement method in telemetered freely moving cynomolgus monkeys: Assessment of an intravascular biopotential lead

被引:8
作者
Authier, S. [1 ,2 ]
Moon, L. B. [3 ]
Stonerook, M. [4 ]
Fournier, S. [1 ]
Gervais, J. [1 ,2 ]
Maghezzi, S. [1 ]
Troncy, E. [2 ]
机构
[1] LAB Res Inc, Laval, PQ H7V 4B3, Canada
[2] Univ Montreal, Fac Med Vet, GREPAQ Dept Vet Biomed, St Hyacinthe, PQ J2S 7C6, Canada
[3] Data Sci Int, St Paul, MN 55112 USA
[4] Verrex Pharmaceut, Cambridge, MA 02139 USA
关键词
Methods; Telemetry; Safety pharmacology; ECG; Cardiovascular; Surgery; SAFETY PHARMACOLOGY;
D O I
10.1016/j.vascn.2011.05.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: 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. Discussion: 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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:145 / 150
页数:6
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