Cyclosporine treatment improves mesenteric perfusion and attenuates necrotizing enterocolitis (NEC)-like intestinal injury in asphyxiated newborn piglets during reoxygenation

Abstract

Asphyxia-related intestinal injury in neonates may present similar to necrotizing enterocolitis (NEC) and is partially associated with hypoxia-reoxygenation injury. Cyclosporine has been shown to reduce myocardial cell death following ischemia-reperfusion. We hypothesize that cyclosporine treatment may attenuate NEC-like intestinal injury in asphyxiated newborn piglets during reoxygenation. Twenty piglets (1-4 days old) were acutely anesthetized and instrumented for continuous monitoring of systemic hemodynamics and superior mesenteric arterial (SMA) flow. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2 h followed by reoxygenation with 100% oxygen for 0.5 h, then 21% for 3.5 h. The piglets were blindly block-randomized to receive cyclosporine (10 mg/kg) or placebo (normal saline) boluses at 5 min of reoxygenation (n = 8/group). A sham-operated group was included (n = 4) and received no hypoxia-reoxygenation. Intestinal samples were collected for tissue lactate and histological assessment (Park's criteria). At 2 h of hypoxia, piglets had cardiogenic shock (cardiac output 45% of baseline), hypotension (mean arterial pressure 30 mmHg), acidosis (pH 7.04), and decreased superior mesenteric perfusion (all P < 0.05 vs. sham-operated group, ANOVA). Cyclosporine treatment increased SMA flow (114 ± 6 vs. 78 ± 19% of baseline of controls, respectively) with improved SMA oxygen delivery and intestinal tissue lactate (all P < 0.05). Some control piglets had NEC-like injuries including pneumatosis intestinalis, which were attenuated in cyclosporine-treated piglets (P < 0.05 vs. controls). This is the first study to demonstrate that post-resuscitation administration of cyclosporine improves mesenteric perfusion and attenuates NEC-like intestinal injury in newborn piglets following asphyxia-reoxygenation.