Regional lung metabolic profile in a piglet model of cardiopulmonary bypass with circulatory arrest.

INTRODUCTION: Acute lung injury is common following cardiopulmonary bypass and deep hypothermic circulatory arrest for congenital heart surgery with the most severe injury in the dorsocaudal lung. Metabolomics offers promise in deducing mechanisms of disease states, providing risk stratification, and understanding therapeutic responses in regards to CPB/DHCA related organ injury. OBJECTIVES: Using an infant porcine model, we sought to determine the individual and additive effects of CPB/DHCA and lung region on the metabolic fingerprint, metabolic pathways, and individual metabolites in lung tissue. METHODS: Twenty-seven infant piglets were divided into two groups: mechanical ventilation + CPB/DHCA (n = 20) and mechanical ventilation only (n = 7). Lung tissue was obtained from dorsocaudal and ventral regions. Targeted analysis of 235 metabolites was performed using HPLC/MS-MS. Data was analyzed using Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA), ANOVA, and pathway analysis. RESULTS: Profound metabolic differences were found in dorsocaudal compared to ventral lung zones by PCA and PLS-DA (R2 = 0.7; Q2 = 0.59; p < 0.0005). While overshadowed by the regional differences, some differences by exposure to CPB/DHCA were seen as well. Seventy-four metabolites differed among groups and pathway analysis revealed 20 differential metabolic pathways. CONCLUSION: Our results demonstrate significant metabolic disturbances between dorsocaudal and ventral lung regions during supine mechanical ventilation with or without CPB/DHCA. CPB/DHCA also leads to metabolic differences and may have additive effects to the regional disturbances. Most pathways driving this pathology are involved in energy metabolism and the metabolism of amino acids, carbohydrates, and reduction-oxidation pathways.

Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest.

Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.

Suspected necrotising enterocolitis after surgery for CHD: an opportunity to improve practice and outcomes.

Infants with CHD are at increased risk of necrotising enterocolitis, which can interfere with the achievement of adequate nutrition and, ultimately, growth and development. Necrotising enterocolitis is classified by severity as suspected, confirmed, and advanced. We sought to quantify the incidence of all types of necrotising enterocolitis among infants who underwent surgery, with a particular focus on suspected necrotising enterocolitis. This is a retrospective review of all infants <6 months of age who underwent cardiac surgery during 2012 and 2013 at Children's Hospital Colorado. We examined the hospital course of 265 hospitalisations (n=251 patients) and found 18 patients (19 hospitalisations) with suspected necrotising enterocolitis and 16 patients (16 hospitalisations) with confirmed or advanced necrotising enterocolitis. Single-ventricle physiology, lower weight, and younger age were associated with necrotising enterocolitis. Patients with all types of necrotising enterocolitis experienced prolonged length of hospital stay. We found suspected necrotising enterocolitis to be as common as confirmed necrotising enterocolitis, and it frequently occurred early in the post-operative course. We speculate that suspected necrotising enterocolitis may often be overlooked in research owing to a reliance on billing codes. Nevertheless, suspected necrotising enterocolitis poses a substantial barrier to post-operative progression of the CHD patient, as does confirmed necrotising enterocolitis. Following the diagnosis of all types of necrotising enterocolitis, there was wide variability in practice patterns. In response to this variability, we developed care guidelines for the diagnosis and treatment of necrotising enterocolitis in this population.