RNA-seq analysis of young swine following cardiac ischemia/reperfusion injury.

This study was a part of a larger study assessing the response of young pigs to cardiac ischemia/reperfusion (IR) injury. A mild cardiac injury approach (IR) was used in post-weaned pigs (1-month), to assess regenerative repair in young large mammals after transient ischemic injury. Female and male postnatal day (P)30 pigs were subjected to cardiac ischemia (1-hour) by occlusion of the left anterior descending artery followed by reperfusion (IR), or to sham operation. In pigs subjected to IR, myocardial damage occurred, indicated by increased circulating cardiac troponin I 2-hours post-ischemia. In addition, cardiac ejection fraction (EF) was significantly decreased 2-hours post-ischemia and reduced EF was maintained to the 4-week study end-point. Histology demonstrated evidence of CM cell cycling at 2-months of age in multinucleated CMs in both sham-operated and IR pigs. Following IR, regional scar formation and inflammation in the epicardial region proximal to injury were observed 4-weeks post-IR. Sex differences in cardiac function and collagen deposition were found, highlighting the importance of representing both sexes in cardiac injury studies. Together, our results describe an effective novel cardiac injury model in 1-month old swine, at a time when CM are still cycling. However, pigs subjected to IR show a prolonged decrease in cardiac function, and the formation of a small, regional scar with increased inflammation. Together, these data demonstrate that 1-month old pigs do not regenerate myocardium, but form a scar, after transient IR injury.