Session S22.5

Applications of Novel HRV Techniques to PGC1a-Deficient and Wild Type Mice

PK Stein*, DW Lee, J Lehman, A Gupta

Washington University
St. Louis, MO, USA

Background: Traditional time and frequency domain heart rate variability (HRV) have been used to understand the effect of various genetic knockouts on autonomic function in different mouse models. Graphical plots of beat-by-beat heart rate patterns, such as Poincaré plots, provide information about heart rate structure that goes beyond traditional HRV. We compared hourly Poincaré plots in wild type and in PGC1a-deficient mice. PGC1a is a transcriptional coactivator that regulates myochondrial energy transduction. Lack of PGC1a reduces the ability of the heart to generate ATP efficiently from fatty acids and glucose via the mitochondria.
Methods: N=8 mice, 4 wild-type and 4 PGC1a knockouts had ECGs collected for 3 minutes from each hour for 24 hours at a sampling rate of 1000 Hz. Recordings were down-sampled by a factor of 12 to reduce the mouse heart rate to human range. Hourly recordings were separately loaded onto a MARS 8000 Holter scanner and analyzed using standard research Holter techniques. Beat-to-beat files were exported, and the interbeat intervals were divided by 12 to restore the original heart rates. Poincaré plots of each normal-to-normal interbeat interval vs. the next were generated for each hour.
Results: Compared to normal mice, PGC1a knockout mice tended to have lower average heart rates (694±16 vs. 752±51 bpm, p=0.076) consistent with impairment in the ability to generate energy efficiently for increases in cardiac heart rate and work. Consistent also, is the separate finding that PGC-1a deficient mice exhibit reduced heart rate increases with treadmill exercise relative to wild-type mice at the same exercise treadmill speed. Examination of the Poincaré plots showed that none of the wild-type mice had abnormal, fan-like, complex patterns in any hour of their recording. However, 3 of the 4 knockout mice had a complex pattern during 10-12 hours of the recording.
Conclusion: Hourly Poincaré plot analyses from short-term recordings are useful in identifying cardiac autonomic abnormalities in knockout mouse models. Samples from the entire 24-hour period provide more information about autonomic function than a single brief recording.

(Abstract Control Number: 135)