Introduction: Abnormal Ca²⁺ handling in ventricular myocytes has been implicated in both contractile dysfunction and arrhythmias in heart failure (HF). We investigated arrhythmogenic Ca²⁺ release in rats with varying degrees of cardiac contractile dysfunction.

Methods: 

Three groups of rats were characterized by echocardiography after myocardial infarction (MI): dilated cardiomyopathy without HF (MI+), congestive HF (CHF), and SHAM-operated controls. Whole cell Ca²⁺ imaging was performed in left ventricular myocytes.

Results: 

At 1, 4 and 8 Hz field stimulation, Ca²⁺ transient amplitude was unaltered in MI+ compared to SHAM, but increased in CHF (P<0.001 for all frequencies). This coincided with sarcoplasmic reticulum (SR) Ca²⁺ content which was unchanged in MI+, but increased in CHF at 4 and 8 Hz (P<0.001) compared to SHAM. However, differences in SR Ca²⁺ content could not be explained by SERCA-dependent Ca²⁺ reuptake which was increased in MI+ (P<0.05 for all frequencies), but unchanged in CHF compared to SHAM. Interestingly, at 1 Hz MI+ exhibited increased fraction of cells with Ca²⁺ waves compared to SHAM (31 vs. 5 %, P<0.05), as well as increased frequency of Ca²⁺ waves per cell (0.07 ± 0.003 vs. 0.005 ± 0.003 waves/s, P<0.05). Surprisingly, CHF had decreased fraction of cells with Ca²⁺ waves at 4 Hz compared to SHAM (22 vs. 48 %, P<0.05), and decreased frequency of Ca²⁺ waves at 8 Hz (0.1 ± 0.02 vs. 0.2 ± 0.03, P<0.05).

Conclusion: 

Post MI rats without HF exhibited increased propensity for Ca²⁺ waves compared to SHAM, whereas no such difference was observed in CHF rats. These findings were not readily explainable from initial characterizations of Ca²⁺ handling. Further investigations are needed to mechanistically explain these differences.