Remote ischemic conditioning in necrotizing enterocolitis

Abstract

Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disorder, most prevalent in premature infants, and associated with a high mortality rate that has remained unchanged in the past two decades. NEC is characterized by inflammation, ischemia, and impaired microcirculation in the intestine. Preclinical studies by our group have led to the discovery of remote ischemic conditioning (RIC) as a promising non-invasive intervention in protecting the intestine against ischemia-induced damage during early-stage NEC. RIC involves the administration of brief reversible cycles of ischemia and reperfusion in a limb (similar to taking standard blood pressure measurement) which activate endogenous protective signaling pathways that are conveyed to distant organs such as the intestine. RIC targets the intestinal microcirculation and by improving blood flow to the intestine, reduces the intestinal damage of experimental NEC and prolongs survival. A recent Phase I safety study by our group demonstrated that RIC was safe in preterm infants with NEC. A phase II feasibility randomized controlled trial involving 12 centers in 6 countries is currently underway, to investigate the feasibility of RIC as a treatment for early-stage NEC in preterm neonates. This review provides a brief background on RIC as a therapeutic strategy and summarizes the progression of RIC as a treatment for NEC from preclinical investigation to clinical evaluation.