Proceedings of The Physiological Society

University of Cambridge (2004) J Physiol 555P, PC10


Phenotypic differences in heart rate and heart rate variability using conscious inbred strains of mice

R. Howden and S.R. Kleeberger

National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Recent studies have suggested a genetic component to heart rate variability (HRV; Singh et al. 2001). Inbred mice are useful to investigate the genetic determinants of complex physiological phenotypes. However, investigation of the genetic determinants of heart rate (HR) and HRV presents methodological difficulties when using a mouse model. It is now possible to avoid the confounding affects anaesthesia on mouse cardiac function (Roth et al. 2001) by recording the electrocardiogram (ECG) using radio telemetry (Data Sciences Int., MN, USA) in conscious mice. While respiration cannot be controlled in conscious mice, it can be monitored using whole body plethysmography (Buxco Electronics Inc., NY, USA). ECG recordings can be timed to coincide with periods of consistent breathing rate and depth. The purpose of this study was to investigate possible differences in resting HR and HRV in C3H/HeJ and NZB/BinJ inbred mice, under conditions of consistent breathing rate and depth.

All procedures were approved by the NIEHS Animal Care and Use Committee and conformed closely to the principles of UK animal legislation. Ten mice per strain (8-10 wks; 20-30g) were anaethetised with inhaled isoflorane, and buprenorphin was given (0.1 mg/kg) for analgesia. A 3.8 g radio telemetry transmitter (Data Sciences Int., MN, USA) was implanted in a dorsal subcutaneous tissue pocket. ECG and respiratory function were recorded from individual mice following at least 30 min of acclimation to the whole body plethysmographs or until breathing rate and depth became consistent. Following data collection mice were euthanised humanely. R waves in the ECG waveform were marked and extracted, and arrhythmias were removed. HRV was assessed in the frequency domain using the Lomb periodogram technique (Laguna et al. 1998). A significant difference was found in resting HR between C3H/HeJ and NZB/BinJ mice (P < 0.001, t test) (Table 1). However, not all HRV parameters were significantly different between strains. Differences were found in total power (TP) and in the high frequency (HF) range (0.2-5.0 Hz and 1.5-5.0 Hz respectively; P < 0.001, ANOVA). HRV in low frequency range was not different between strains (0.2-1.5 Hz; P > 0.05, ANOVA).

Using the above techniques we identified phenotypic differences in HR and HRV. These results provide evidence for a genetic component in the regulation of resting HR and HRV. Positional cloning is required to assess the extent to which genes contribute to HR and HRV.

Where applicable, experiments conform with Society ethical requirements