The Slow Force Response and Simultaneous Changes in Ca2+ Transient in Healthy and Failing Rat Atrial and Ventricular Myocardium

The Slow Force Response (SFR) is an important mechanism of adaptation of myocardial contractility to the mechanical load. The discrepancies between the SFR in atrial and ventricular myocardium are poorly characterized; moreover, the correlation between the mechanical response and underlying changes in Ca2+ transient are unknown. We measured simultaneous slow changes in force and Ca2+ transient developed in right atrial and ventricular (RA and RV) muscles of healthy rats (CONT) and rats with monocrotaline-induced pulmonary heart failure (MCT) as a response to rapid muscle stretch. The SFR was positive in RA muscles but negative in RV muscles in CONT and MCT groups. The extent of SFR was significantly higher in the failing myocardium. The slow changes in peak active force showed little correlation with rate- and time-related characteristics of isometric force. The relative changes in Ca2+ transient diastolic level, amplitude, time-to-peak and time to decay from peak to 50% amplitude in the end of SFR were significantly smaller compared to the extent of SFR. Plotting the extent of SFR as peak active force vs the extent of change in Ca2+ transient diastolic level or amplitude revealed that only the latter was followed nearly linear behavior while the former had no substantial correlation. We conclude that the minor changes in Ca2+ transient characteristics during SFR underlie the much greater changes observed in the peak active force. The atrioventricular discrepancies in the SFR indicate different adaptive responses of the contractility of these chambers to the external mechanical loading.