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 ofadaptation of myocardial contractility to the mechanical load. Thediscrepancies between the SFR in atrial and ventricular myocardiumare poorly characterized; moreover, the correlation between themechanical response and underlying changes in Ca2+ transientare unknown. We measured simultaneous slow changes in force andCa(2+) transient developed in right atrialand ventricular (RA and RV) muscles of healthy rats (CONT) and ratswith monocrotaline-induced pulmonary heart failure (MCT) as a responseto rapid muscle stretch. The SFR was positive in RA muscles butnegative in RV muscles in CONT and MCT groups. The extent of SFRwas significantly higher in the failing myocardium. The slow changesin peak active force showed little correlation with rate- and time-related characteristicsof isometric force. The relative changes in Ca2+ transientdiastolic level, amplitude, time-to-peak and time to decay frompeak to 50% amplitude in the end of SFR were significantly smallercompared to the extent of SFR. Plotting the extent of SFR as peakactive force vs the extent of change in Ca2+ transientdiastolic level or amplitude revealed that only the latter was followed nearlylinear behavior while the former had no substantial correlation.We conclude that the minor changes in Ca2+ transientcharacteristics during SFR underlie the much greater changes observed inthe peak active force. The atrioventricular discrepancies in theSFR indicate different adaptive responses of the contractility ofthese chambers to the external mechanical loading.

Automated summary

The Slow Force Response (SFR) is an important mechanism for myocardial contractility adaptation. The discrepancies between atrial and ventricular SFR and the correlation between mechanical response and Ca2+ transient changes are poorly characterized. Our study found that the extent of SFR was higher in failing myocardium, and the changes in Ca2+ transient characteristics were smaller compared to the extent of SFR.