Force-frequency (FFR) and relaxation-frequency relationships (RFR) and post-extrasystolic potentiation (PESP) reflect changes in Ca2+ cycling by sarcoplasmic reticulum (SR) & sarcolemma (SL). In immature animals, effects of pacing-induced heart failure on these physiologic indices is unknown. We studied FFR, RFR and PESP in 6 young goats (Age: 4 wks), paced at 300 bpm for prior 2.5 weeks (P) & 5 age matched controls (C). LV dP/dtmax & time constant of relaxation (τ) were calculated from micromanometric tracings at increasing heart rates (HR) generated by right atrial pacing. HR at which pulsus alternans appeared was defined as“Critical HR” (HRcrit). PESP was studied at constant cycle length & extrasystole & post-extrasystole introduced at 300 ms and 700 ms, respectively. Parameters were remeasured after ryanodine, a SR Ca2+ channel release blocker (5 μg/kg). HRcrit was significantly lower in P group (221±34.5 vs 280±24.8 bpm, p<0.05, Fig. 1). Following ryanodine, HRcrit was lowered in C group but did not drop significantly in P group (192.5±18.4 vs 221±34.5 bpm, p<0.05), suggesting alternate sources of activator Ca2+ in P. In both P and C groups, there was no or mild PESP (0-10%), possibly due to faster recirculation of Ca2+ through SR of young animals. Faster recirculation of Ca2+ may be responsible for faster restitution of contractility, leading to less PESP. Following ryanodine, PESP was decreased (30-34%) in both groups.

Fig. 1
figure 1

Force-frequency (A) and relaxation-frequency (B) relationships in C (•) and P (▪) groups.

Full size image

Conclusions: In pacing-induced heart failure induced in immature animals, SR function decreases suggested by decreased HRcrit and shifts in FFR and RFR curves. Blockade of SR Ca2+ release by ryanodine, not only decreases force of contraction, but impairs relaxation due to Ca2+ dependency of SR Ca2+ reuptake. These physiologic indices act as mirrors and provide unique insight into Ca2+ handling by SR of immature animals.