AIM: Left ventricular pressure overload (LVPO) in adults is associated with adverse electrical remodeling, characterized by reduced conduction velocity (CV). However, the progression of LVPO differs when imposed during the proliferative phase of cardiac development. It remains unknown how increased cardiomyocyte proliferation affects LVPO electrical remodeling. METHODS: CV maturation from rat postnatal day (PD) 1 to PD90 and analyzed underlying connexin 43 (Cx43) profile. Pressure overload was induced by abdominal aortic constriction (AAC) in rats during the proliferative phase of cardiac growth (PD2). Animals subjected to AAC during the non-proliferative heart growth (AAC-PD6) and Sham-operated rats served as controls. Electrical remodeling was assessed at PD21 using ECG, optical mapping, western blots, immunofluorescence, and lipidomic analysis, complemented by functional analyses through echocardiography. RESULTS: Pressure overload led to a 2.5-fold increase in heart weight compared to Sham in both AAC groups. A significant increase in relative left ventricular wall thickening was observed in AAC-PD2 rats only. Optical mapping and ECG showed preserved conduction properties in AAC-PD2 animals, whereas the AAC-PD6 group displayed prolonged QRS and significantly reduced longitudinal CV. While total and phosphorylated Cx43 levels were comparable between the AAC groups, AAC-PD2 animals demonstrated higher intercalated disc localization. Furthermore, lipidomic profiling revealed maintained long-chain acylcarnitine (LCAC) levels in AAC-PD2, whereas AAC-PD6 tended toward LCAC accumulation. CONCLUSION: This study provides new insights into the remodeling upon pressure overload during cardiac proliferative growth, demonstrating attenuated electrical alteration by preserved CV and highlighting the role of Cx43 localization and preserved levels of LCACs.

1st Faculty of Medicine Institute of Anatomy Charles University Prague Czech Republic

Centre for Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

Czech Centre for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences Vestec Czech Republic

Department of Biochemistry and Microbiology University of Chemistry and Technology Prague Czech Republic

Institute of Physiology Czech Academy of Sciences Prague Czech Republic

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