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J Physiol Volume 534, Number 2, 535-545, July 15, 2001
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Journal of Physiology (2001), 534.2, pp. 535-545
© Copyright 2001 The Physiological Society

Minimal force-frequency modulation of inotropy and relaxation of in situ murine heart


Dimitrios Georgakopoulos and David A. Kass


Division of Cardiology, Department of Medicine and Department of Biomedical Engineering, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

  1. The normal influence of heart rate (HR) on cardiac contraction and relaxation in the mouse remains uncertain despite its importance in interpreting many genetically engineered models. Prior in vivo data have repeatedly shown positive effects only at subphysiological heart rates, yet depressed basal conditions and use of load-dependent parameters probably have an impact on these results.
  2. Open-chest mice of various strains (n = 16, etomidate/urethane anaesthesia) were instrumented with a miniaturized pressure-volume catheter employing absolute left ventricular (LV) volume calibration. HR was slowed (< 400 beats min-1) using ULFS-49, and atrial or ventricular pacing was achieved via an intra-oesophageal catheter. Pressure-volume data yielded cardiac-specific contractile indexes minimally altered by vascular load.
  3. At a resting HR of 600 beats min-1, peak pressure-rise rate (dP/dtmax) was 16 871 ± 2941 mmHg s-1 (mean ± S.D.) and the relaxation time constant was 3.9 ± 0.8 ms, similar to values in conscious animals. Within the broad physiological range (500-850 beats min-1), load-insensitive contractile indexes and relaxation rate varied minimally, whereas dP/dtmax peaked at 600 ± 25 beats min-1 and decreased at higher rates due to preload sensitivity. Contraction and relaxation were enhanced modestly (13-15 %) at HRs of between 400 and 500 beats min-1.
  4. The minimal force-frequency dependence was explained by rapid calcium cycling kinetics, with a mechanical restitution time constant of 9 ± 2.7 ms, and by dominant sarcoplasmic reticular buffering (recirculation fraction of 93 ± 1 %).
  5. The mouse normally has a very limited force-frequency reserve at physiological HRs, unlike larger mammals and man. This is important to consider when studying disease evolution and survival of genetic models that alter calcium homeostasis and SR function.



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