Fig. 3: Intramyocardially injected hPKM2 CM SMRTs improved cardiac function and reduced infarct size in an I/R model using Juvenile Yorkshire pigs.
a Experimental timeline to evaluate cardiac function and outcome in an acute I/R porcine model using juvenile Yorkshire pigs. Echocardiographic images (b) obtained from pigs in the hPKM2 CM SMRTs and vehicle groups before balloon occlusion (Day −7), before injection (Day 0), and 10 and 56 days after intervention. These images were used to calculate (c) %EF and (d) %FS. Cardiac magnetic resonance imaging (e, cMRI) was performed on Day 56 and used to calculate (f) %EF, (g) stroke volume, h end-systolic volume, and (i) end-diastolic volume. Sixteen-segment curves corresponding to (j) radial strain (εrr) and (k) LV wall thickening (%LVWT) on Day 56 after intervention. Calculation of the (l) area under the curve (AUC) in arbitrary units for εrr and (m) LVWT at different heart segments. (n) Representative images of LVs collected on Day 56 and cut into five circular sections from the apex to the base (see Supplementary Fig. 4a for all collected images). Late gadolinium enhancement cardiac MRI (LGE-cMRI) images were obtained from pigs 1 day before (Day −1) and 56 days after (Day 56) injection. (o) Representative LGE-cMRI images from one vehicle-treated and one hPKM2 CM SMRTs-treated animal, acquired on Day −1 and Day 56. The endocardium is contoured in red, the epicardium in blue, and the infarct area in yellow. LGE-cMRI images were used to calculate infarct (p) volume and (q) infarct size. n = 10 biological replicates (pigs) per group unless otherwise stated; unit of study = pig. For (c, d), data points represent group means at each time point; error bars indicate SEM from n = 10 pigs/group. For (f–k), each dot represents one pig (n = 10/group); data are presented as mean ± SEM. For (l, m), data points represent group means for each heart segment; error bars indicate SEM from n = 10 pigs/group. For (p, q), each dot represents one pig; n = 3/group at Day −1 and n = 10/group at Day 56; data are presented as mean ± SEM. Scale bar = 2 cm. Two-way ANOVA with Tukey’s multiple comparison test for (c, d, l, m, p, q); unpaired two-tailed t-test for (f–k). *P < 0.05; **P < 0.01; ****P < 0.0001; N.S., not significant. For additional statistical information, see Supplementary data 1. Panel (a) Created in BioRender. Zangi, L. (2025) https://BioRender.com/t1c39vu.
