Calcium handling in postinfarction arrhythmias: evidence from large animals.

Understanding the causes of ventricular arrhythmias after myocardial infarction (MI) remains a major challenge to academic and clinical medicine. Key concepts in the pathophysiology underlying such events are based on studies in rodents, in whom altered sarcoplasmic reticulum (SR) calcium handling is key even in chronic stages after MI. Since cardiac electrophysiology in rodents has important differences from humans, an overview of insights directly from large animals and humans is needed. Our objective was to provide a summary of existing literature on the role of SR calcium handling in ventricular tachyarrhythmias after the acute phase of MI in large animals and humans. We conducted a systematic search of original articles on calcium handling after MI in large animals and humans, summarized key findings, and assessed risk of bias in the included articles. Twenty-five studies explicitly measuring cellular calcium handling after MI in large animals or human tissue were included. Overall, the studies were somewhat ambiguous regarding calcium transient amplitude and kinetics, but consistently showed increased frequency of calcium sparks, calcium waves, delayed afterdepolarizations, and reduced t-tubule density, while some reported increased propensity for calcium alternans. Abundance and posttranslational modification of calcium handling proteins were less consistent. In conclusion, existing evidence from large animals and human material supports a role for altered calcium handling in ventricular arrhythmias after MI. However, the evidence is still limited. More studies in such models are needed to provide mechanistic explanations that can be used as a basis for development of new therapies.