(A) Partial apex resection surgery performed on neonatal piglets. Inserted image schematically shows the partial apex resection location. (B) Heart muscle tissue resected from the apex of a piglet heart. (C) Piglets resting with mother sow after surgery.

Average ejection fraction (percentage) at different time points for each group. (A) Zero-day control group. (B) Zero-day surgery group. (C) seven-day control group. (D) seven-day surgery group. *, **, and *** represent a significant difference (p < 0.05) between before surgery and the labeled time point.

Average fractional shortening (percentage) at different time points for each group. (A) Zero-day control group. (B) Zero-day surgery group. (C) Seven-day control group. (D) Seven-day surgery group. * and ** represent a significant difference (p < 0.05) between before surgery and the labeled time point.

Gross anatomy photos. (A) Zero-day control (sham) heart from piglet #2033. (B) Zero-day control (sham) heart from piglet #2038. (C) Zero-day surgery heart from piglet #2034. (D) Zero-day surgery heart from piglet #2035. (E) Zero-day surgery heart from piglet #2036. (F) Zero-day surgery heart from piglet #2037. Scale bar = 1 cm.

Gross anatomy photos. (A) Seven-day control (sham) heart from piglet #2071. (B) Seven-day control (sham) heart from piglet #2077. (C) Seven-day surgery heart from piglet #2073. (D) Seven-day surgery heart from piglet #2075. (E) Seven-day surgery heart from piglet #2076. Scale bar = 1 cm.

Partial apex resection surgery at 0 days and heart explanted at 4W PO-Masson’s Trichrome histology of 0-day control hearts and 0-day surgery hearts. Heart explants were obtained four weeks post-operation (4W PO). (A) Zero-day control (sham) heart from piglet #2033. (B) Zero-day control (sham) heart from piglet #2038. (C) Zero-day surgery heart from piglet #2034. (D) Zero-day surgery heart from piglet #2035. (E) Zero-day surgery heart from piglet #2036. (F) Zero-day surgery heart from piglet #2037. Histological images were taken at 4× magnification (Scale bar = 200 μm). Masson’s Trichrome: red–muscle; blue–collagen.

Partial apex resection surgery at 0 days and heart explanted at 4W PO-Hematoxylin and Eosin (H & E) histology of 0-day control hearts and 0-day surgery hearts. Heart explants were obtained four weeks post-operation (4W PO). (A) Zero-day control (sham) heart from piglet #2033. (B) Zero-day control (sham) heart from piglet #2038. (C) Zero-day surgery heart from piglet #2034. (D) Zero-day surgery heart from piglet #2035. (E) Zero-day surgery heart from piglet #2036. (F) Zero-day surgery heart from piglet #2037. Histological images were taken at 4× magnification (Scale bar = 200 μm). H & E: pink–cytoplasm; blue–nuclei; intense red–erythrocytes.

Partial apex resection surgery at seven days and heart explanted at 4W PO-Masson’s Trichrome histology of seven-day control hearts and seven-day surgery hearts. Heart explants were obtained four weeks post-operation (4W PO). (A) Seven-day control (sham) heart from piglet #2071. (B) Seven-day control (sham) heart from piglet #2077. (C) Seven-day surgery heart from piglet #2073. (D) Seven-day surgery heart from piglet #2075. (E) Seven-day surgery heart from piglet #2076. Histological images were taken at 4× magnification (Scale bar = 200 μm). Masson’s Trichrome: red–muscle; blue–collagen.

Partial apex resection surgery at seven days and heart explanted at 4W PO-Hematoxylin and Eosin (H & E) histology of seven-day control hearts and seven-day surgery hearts. Heart explants were obtained four weeks post-operation (4W PO). (A) Seven-day control (sham) heart from piglet #2071. (B) Seven-day control (sham) heart from piglet #2077. (C) Seven-day surgery heart from piglet #2073. (D) Seven-day surgery heart from piglet #2075. (E) Seven-day surgery heart from piglet #2076. Histological images were taken at 4× magnification (Scale bar = 200 μm). H & E: pink–cytoplasm; blue–nuclei; intense red–erythrocytes.

Partial apex resection surgery at 0 day and heart explants at 5D PO and 1W PO-Masson’s Trichrome histology of 0-day surgery heart explants obtained five days post-operation (5D PO): (A) Zero-day surgery heart from piglet #004. (B) Zero-day surgery heart from piglet #015. (C) Zero-day surgery heart from piglet #014. (D) Zero-day surgery heart from piglet #013. Masson’s Trichrome histology of 0-day surgery heart explants obtained one-week post-operation (1W PO): (E) Zero-day surgery heart from piglet #001. (F) Zero-day surgery heart from piglet #024. (G) Zero-day surgery heart from piglet #002. (H) Zero-day surgery heart from piglet #018. Histological images were taken at 4× magnification (Scale bar = 200 μm). Masson’s Trichrome: red–muscle; blue–collagen.

Partial apex resection surgery at 0 day and heart explants at 5D PO and 1W PO-Hematoxylin and Eosin (H & E) histology of 0-day surgery heart explants obtained five days post-operation (5D PO): (A) Zero-day surgery heart from piglet #004. (B) Zero-day surgery heart from piglet #015. (C) Zero-day surgery heart from piglet #014. (D) Zero-day surgery heart from piglet #013. H & E histology of 0-day surgery heart explants obtained one-week post-operation (1W PO): (E) Zero-day surgery heart from piglet #001. (F) Zero-day surgery heart from piglet #024. (G) Zero-day surgery heart from piglet #002. (H) Zero-day surgery heart from piglet #018. Histological images were taken at 4× magnification (Scale bar = 200 μm). H & E: pink–cytoplasm; blue–nuclei; intense red–erythrocytes.

Partial apex resection surgery at 0 days and heart explanted at 5D PO (A–C)—(A) Gross necropsy heart obtained five days post-operation (5D PO) from piglet #004. Note partially filled surgical defect (blue arrow) (Scale bar = 1 cm). (B) Hematoxylin and Eosin (H & E) histology (piglet #004) reveals a densely packed population of streaming cells in register with peripheral myocardium and with similar slightly larger elongate often plump nuclei (Scale bar = 20 μm). (C) H & E histology (piglet #004) of the marginal zone of proliferative cells has a mitotic figure of a cell identifiable as a cardiomyocyte based on straplike morphology, eosinophilic cytoplasm, and cross striations (black arrows) (Scale bar = 20 μm). Partial apex resection surgery at 0 days and heart explanted at 5D PO (D–F)—(D) Gross necropsy heart obtained five days post-operation (5D PO) from piglet #015. Note partially filled surgical defect (blue arrow) (Scale bar = 1 cm). (E) H & E histology (piglet #015) reveals a population of similar streaming elongate cells with elongate nuclei. (F) Masson’s trichrome stain (piglet #015) reveals a moderate intervening collagenous matrix.

Partial apex resection surgery at 0 days and heart explanted at 1W PO-(A) Hematoxylin and Eosin (H & E) histology 0-day surgery heart explant obtained one week post-operation (1W PO) from piglet #018. Higher magnification of the field of Figure 11H reveals proliferative spindle cells with thin nuclei often oriented in stacked arrays (black arrow) that are perpendicular to capillaries (blue arrow) typical of fibrovascular tissue. The relationship to the myocardium is abrupt. (B) Masson’s Trichrome of the same field reveals prominent interspersed collagen (Scale bar = 50 μm).

Partial apex resection surgery at seven days and heart explants at 5D PO and 1W PO-Masson’s Trichrome histology of seven-day surgery heart explants obtained five days post-operation (5D PO): (A) Seven-day surgery heart from piglet #007. (B) Seven-day surgery heart from piglet #008. (C) Seven-day surgery heart from piglet #029. (D) Seven-day surgery heart from piglet #031. Masson’s Trichrome histology of seven-day surgery heart explants obtained one week post-operation (1W PO): (E) Seven-day surgery heart from piglet #009. (F) Seven-day surgery heart from piglet #010. (G) Seven-day surgery heart from piglet #016. (H) Seven-day surgery heart from piglet #028. Histological images were taken at 4× magnification (Scale bar = 200 μm). Masson’s Trichrome: red–muscle; blue–collagen.

Partial apex resection surgery at seven days and heart explants at 5D PO and 1W PO-Hematoxylin and Eosin (H & E) histology of seven-day surgery heart explants obtained five days post-operation (5D PO): (A) Seven-day surgery heart from piglet #007. (B) Seven-day surgery heart from piglet #008. (C) Seven-day surgery heart from piglet #029. (D) Seven-day surgery heart from piglet #031. H & E histology of seven-day surgery heart explants obtained one-week post-operation (1W PO): (E) Seven-day surgery heart from piglet #009. (F) Seven-day surgery heart from piglet #010. (G) Seven-day surgery heart from piglet #016. (H) Seven-day surgery heart from piglet #028. Histological images were taken at 4× magnification (Scale bar = 200 μm). H & E: pink–cytoplasm; blue–nuclei; intense red–erythrocytes.

Histological images stained with H & E for the 0-day piglet (#2039) that was accidentally killed by the mother sow three days post apex resection surgery. (A) Image of 0-day piglet heart at 2× magnification; (B) Image of 0-day piglet heart at 4× magnification; the yellow arrow is the border zone of the dense cellular population; the red arrow is fibrin zone/fibrin; the blue arrow is necrotic cardiomyocytes; scale bar = 200 μm. (C) Image of 0-day piglet heart at 20× magnification; (D) Image of 0-day piglet heart at 20× magnification; scale bar = 20 μm. (E) Image of 0-day piglet heart at 40× magnification; (F) Image of 0-day piglet heart at 40× magnification; the green arrow is cells with mitotic events; the yellow arrow indicates the cells resembling immature cardiomyocytes; scale bar = 20 μm. H & E: pink–cytoplasm; blue–nuclei; intense red–erythrocytes.