Remote Ischemic Conditioning (RIC) Decreases the Incidence and Severity of Necrotizing Enterocolitis (NEC) - Validation in a Large Animal Model

Rahul Gadde; Jason Xia; Sophia Hameedi; Angela Saulsbery; Carly Schafer; Lourenço Sbragia; Oluyinka O Olutoye

doi:10.1016/j.jpedsurg.2024.161957

Remote Ischemic Conditioning (RIC) Decreases the Incidence and Severity of Necrotizing Enterocolitis (NEC) - Validation in a Large Animal Model

J Pediatr Surg. 2024 Sep 24:161957. doi: 10.1016/j.jpedsurg.2024.161957. Online ahead of print.

Authors

Rahul Gadde¹, Jason Xia¹, Sophia Hameedi¹, Angela Saulsbery¹, Carly Schafer¹, Lourenço Sbragia¹, Oluyinka O Olutoye²

Affiliations

¹ Center for Regenerative Medicine - Abigail Wexner Research Institute, and Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA.
² Center for Regenerative Medicine - Abigail Wexner Research Institute, and Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA; Division of Pediatric Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: oolutoye@nationwidechildrens.org.

PMID: 39368858
DOI: 10.1016/j.jpedsurg.2024.161957

Abstract

Background: Necrotizing enterocolitis (NEC) remains a devastating intestinal disease that affects 5-7% of preterm neonates. Remote ischemic conditioning (RIC) has been shown to protect against intestinal ischemia in rodents. We aimed to determine the efficacy of RIC in a large animal model of NEC.

Methods: Using an established piglet model of NEC, preterm piglets of 103-107 days gestation (term = 115 days) were randomly assigned to receive RIC or serve as untreated controls. RIC was initiated at 24 h of life and consisted of 4 cycles of 4-min occlusion followed by reperfusion; cycles were repeated every 24 or 12 h for low frequency (LF) and high frequency (HF) groups, respectively. Piglets were monitored clinically for NEC which was confirmed postmortem using established anatomic and histologic scoring.

Results: Eighty-six piglets were randomized into controls (N = 38), LF-RIC (n = 26) and HF-RIC (n = 22) groups. In contrast to the rodent models, in piglets LF-RIC (every 24 h) did not decrease the incidence of NEC compared to controls. However, HF-RIC (every 12 h) significantly reduced the incidence of NEC (OR = 0.13; 95% CI: 0.03, 0.55; p = 0.02) and resulted in a lower severity of NEC (p < 0.0001) compared to controls.

Conclusions: RIC offers protection against NEC in the piglet model only when administered more frequently than in rodents. Further studies are needed to define the optimum frequency of RIC for piglets that may translate to clinical use.

Keywords: Animal model; Enteral nutrition; Necrotizing enterocolitis; Piglet; Remote ischemic conditioning.