An interesting article evaluating the scar formation and cardiac function in pig heart after ischemia/reperfusion (IR) injury. Researchers used CHPs in this study to evaluate the damage immediately following IR and even compared this with Masson's Trichrome staining. They found that immediately after IR, the heart does see a decrease in cardiac function in terms of ejection fraction and fractional shortening but that these conditions did not worsen after the initial decrease when evaluated a month later. CHPs helped identify the scar formation on the myocardium and researchers could quantify what percent of collagen was being remodeled relative to the tissue area after IR. This result corroborated the results obtained from Masson's Trichrome staining. They concluded that the injury response in young swine after postnatal period includes inflammation and scarring but no cardiomyocyte renewal despite the presence of mitotic activity in cardiomyocytes.

Figure 7: (B) Representative Masson’s trichrome staining (myocardium = pink, collagen = blue), in sham-operated and IR scar region sections. The arrow depicts obvious scar formation in IR pigs, with arrowheads showing interstitial collagen in sham-operated and IR myocardial sections. (C) Representative images in sham and IR scar zone of immunohistochemistry for collagen hybridizing peptide (CHP, 3Helix), marking remodeling collagen (red) alongside DAPI for nuclei (blue). The arrow depicts dense scar area, with arrowheads indicating interstitial remodeling collagen (red). (F) Quantification of average CHP deposition at 2 months of age across all 3 zones of sham and IR pigs, as well as unoperated control myocardial tissue sections. CHP (red) was measured relative to tissue area (µm2) and displayed as a percentage. (G) The area of CHP reactivity per total area in the epicardial region of each zone was also quantified. Data are mean ± SD. Two-way ANOVA analysis with Tukey post-hoc analysis, * p < 0.05, ** p < 0.01 n = 4–8/group. Scale bar = 50 µm (B), 20 µm (C).

Abstract: Studies in mice show a brief neonatal period of cardiac regeneration with minimal scar formation, but less is known about reparative mechanisms in large mammals. A transient cardiac injury approach (ischemia/reperfusion, IR) was used in weaned postnatal day (P)30 pigs to assess regenerative repair in young large mammals at a stage when cardiomyocyte (CM) mitotic activity is still detected. Female and male P30 pigs were subjected to cardiac ischemia (1 h) by occlusion of the left anterior descending artery followed by reperfusion, or to a sham operation. Following IR, myocardial damage occurred, with cardiac ejection fraction significantly decreased 2 h post-ischemia. No improvement or worsening of cardiac function to the 4 week study end-point was observed. Histology demonstrated CM cell cycling, detectable by phospho-histone H3 staining, at 2 months of age in multinucleated CMs in both sham-operated and IR pigs. Inflammation and regional scar formation in the epicardial region proximal to injury were observed 4 weeks post-IR. Thus, pigs subjected to cardiac IR at P30 show myocardial damage with a prolonged decrease in cardiac function, formation of a regional scar, and increased inflammation, but do not regenerate myocardium even in the presence of CM mitotic activity.


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