Incidence of spontaneous arrhythmias in freely moving healthy untreated Sprague-Dawley rats.
J Pharmacol Toxicol Methods
; 99: 106589, 2019.
Article
in En
| MEDLINE
| ID: mdl-31154034
ABSTRACT
Spontaneous arrhythmia characterization in healthy rats can support interpretation when studying novel therapies. Male (nâ¯=â¯55) and female (nâ¯=â¯40) Sprague-Dawley rats with telemetry transmitters for a derivation II ECG. Arrhythmias were assessed from continuous ECG monitoring over a period of 24-48â¯h, and data analyzed using an automated detection algorithm with 100% manual over-read. While a total of 1825 spontaneous ventricular premature beats (VPB) were identified, only 7 rats (or 7.4%) did not present with any over the recording period. Spontaneous episode(s) of ventricular tachycardia (VT) were noted in males (27%) and females (3%). The incidence of VPB was significantly higher (pâ¯<â¯0.01) during the night time (7â¯pm-7â¯am) compared to daytime, while males presented with significantly (pâ¯<â¯0.001) more VPB than females. Most VPB were observed as single ectopic beats, followed by salvos (2 or 3 consecutive VPBs), and VT (i.e. 4 consecutive VPBs). Most VPBs were single premature ventricular contractions (PVCs) (57%), while the remaining were escape complexes (43%). Spontaneous premature junctional complexes (PJC) were also observed and were significantly more frequent during the night, and in males. Lastly, 596 episodes of spontaneous 2nd-degree atrioventricular (AV) block were identified and were significantly more frequent during the day time in males. Most 2nd-degree AV block episodes were Mobitz type I (57%), with a significantly (pâ¯<â¯0.05) higher incidence in males. This work emphasizes the importance of obtaining sufficient baseline data when undertaking arrhythmia analysis in safety study and provides a better understanding of both sex- and time- dependent effects of spontaneous arrhythmias in rats.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Guideline
/
Incidence_studies
/
Risk_factors_studies
Language:
En
Journal:
J Pharmacol Toxicol Methods
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Canada