Work

Glucose restriction reduces systemic, but not cardiac, inflammation during neonatal sepsis in preterm pigs

Year: 2026

Type: preprint

Abstract: Introduction Preterm infants are highly susceptible to sepsis and hyperglycemia may exacerbate inflammation and worsen outcomes. We examined how glucose provision influences systemic and cardiac responses during neonatal sepsis in preterm pigs. Methods Preterm piglets (90 % gestation) were infused with Staphylococcus epidermidis to induce sepsis. In Experiment 1, three ventilated and anesthetized piglets were continuously monitored for mean arterial pressure (MAP) and blood gases to characterize acute cardiovascular and metabolic deterioration. In Experiment 2, thirty-three piglets were randomized to standard (14 g/kg/day) or reduced (3.5 g/kg/day) glucose provision, with or without infection, and followed for 20h. Results Infection in Experiment 1 caused progressive hypotension, acidosis, and hypoxia, mirroring clinical neonatal sepsis. In Experiment 2, reduced glucose provision improved survival (77 % vs 46 %, p = 0.06) and attenuated systemic inflammation, with lower IL-6 and higher IL-10 concentrations. Infection induced mild cardiac neutrophil infiltration, without affecting plasma troponin T but clearly reduced cardiomyocyte mitotic density and triggered upregulation of inflammatory transcriptional pathways (NF-κB, JAK-STAT) and suppression of oxidative phosphorylation. In infected animals. glucose restriction preserved cardiomyocyte mitotic density but did not alter cardiac structure, injury markers or gene expression. Conclusion Neonatal infection induced circulatory failure, suppression of cardiomyocyte proliferation and upregulation of inflammatory genes in cardiac tissue, while reduced glucose provision mitigated systemic immune responses and preserved cardiomyocyte proliferation.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.10.14.759031