Gadde Rahul, Xia Jason, Hameedi Sophia, Saulsbery Angela, Schafer Carly, Sbragia Lourenço, Olutoye Oluyinka O
Center for Regenerative Medicine - Abigail Wexner Research Institute, and Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA.
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.
J Pediatr Surg. 2025 Jan;60(1):161957. doi: 10.1016/j.jpedsurg.2024.161957. Epub 2024 Sep 24.
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.
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.
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.
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.
坏死性小肠结肠炎（NEC）仍然是一种严重的肠道疾病，影响5%-7%的早产儿。远程缺血预处理（RIC）已被证明可保护啮齿动物免受肠道缺血损伤。我们旨在确定RIC在NEC大型动物模型中的疗效。
使用已建立的NEC仔猪模型，将妊娠103-107天（足月=115天）的早产仔猪随机分为接受RIC组或作为未治疗的对照组。RIC在出生后24小时开始，包括4个周期，每个周期4分钟阻断后再灌注；低频（LF）组和高频（HF）组分别每24小时或12小时重复一次周期。对仔猪进行临床监测以观察NEC，死后通过既定的解剖和组织学评分进行确诊。
86只仔猪被随机分为对照组（N=38）、低频RIC组（n=26）和高频RIC组（n=22）。与啮齿动物模型不同，在仔猪中，低频RIC（每24小时）与对照组相比并未降低NEC的发生率。然而，高频RIC（每12小时）与对照组相比显著降低了NEC的发生率（OR=0.13；95%CI：0.03，0.55；p=0.02），并导致NEC的严重程度较低（p<0.0001）。
只有当给药频率高于啮齿动物时，RIC才能在仔猪模型中提供对NEC的保护。需要进一步研究确定可能转化为临床应用的仔猪RIC最佳频率。
