Chronoinotropic Effects in Langendorff Perfused Rat Heart

If healthy heart responds by an increase of contractility to the acceleration of rhythm then negative force-frequency relationship (FFR) is developed in failed heart. In experimental conditions in perfused rat heart it is possible to obtain the positive as well as negative FFR. Transient force response has been poorly described in details, but FFR have been considered mostly as steady state phenomenon. The aim of the investigation was to study FFR in whole rat heart under different experimental conditions using analysis of force transient response; to study the effect of different extracellular calcium concentrations on force transition dynamics, and hence the resulting sign of chrono-inotropic relation. Materials and methods. On total of 15 Langendorff perfused hearts obtained from Wistar rats, we demonstrated different calcium concentrations ([Ca2+]o) in Krebs–Henseleit buffer to be able to affect FFR in these hearts. Results. There was found that the transient responses have biphasic structure, where first beat (B1) and extremum beat (Bex) can be found. The transient response after step pacing period change can be rather long (sometimes more than 180–300 s); and one should be careful when choosing the duration of pacing protocols. The negative FFR (at 60 s — B60s) is easily modulated by external [Ca2+]o and the parameters of force transient response B1 and Bex are more sensitive (then B60s) to experimental conditions. The increase of intracellular Сa2+ with the help of Ouabain (50 uM) does not affect chrono-inotropic relations in perfused heart of rats. Conclusion. Calcium concentration in perfusion solution was found to be able to affect the dynamics of force transient response after step change in pacing frequency and change the resulting sign of FFR. Intracellular calcium does not significantly change the sign of chrono-inotropic relations.