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

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s11306-021-01842-y.

Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury

“…Frozen tissue samples were extracted according to a previously published protocol ( 36 ). Frozen samples were ground with a tissue grinder in 500 µL of ice-cold methanol-water [80/20 (vol/vol)], sonicated for 10 min, incubated for 4 h at −80°C for protein precipitation, and centrifuged at 14,000 g for 20 min at 4°C.…”

“…We have recently developed a pediatric pig model of CPB with deep hypothermic circulatory arrest (DHCA) in which to study postoperative multiorgan injury, including AKI ( 35 ). The model has been shown to induce significant metabolic changes in the lung ( 36 ), but the metabolic changes in the kidney and their association with AKI have not been defined. Furthermore, the relationship among tissue, circulating, and urinary metabolic profiles is not known.…”

The potential value of cuprotosis in myocardial immune infiltration that occurs in pediatric congenital heart disease in response to surgery with cardiopulmonary bypass

“…Despite the substantial risk of postoperative inflammation and organ injury, CPB are becoming more and more popular in treating congenital heart defects. [19][20][21][22][23][24] Clinically unfavorable outcomes of cardiopulmonary bypass might range from minor symptoms to life-threatening complications and heart failure and low cardiac output syndrome is the most severe consequence. 25 Conventional myocardial protection during surgical procedures focuses on reducing the inflammatory response 26 which is consistent with our enrichment analysis results.…”

“…In our study, we explore the likely function of immune infiltration and genes related with cuproptosis in heart tissue injury following CPB for the first time. Despite the substantial risk of postoperative inflammation and organ injury, CPB are becoming more and more popular in treating congenital heart defects 19–24 . Clinically unfavorable outcomes of cardiopulmonary bypass might range from minor symptoms to life‐threatening complications and heart failure and low cardiac output syndrome is the most severe consequence 25 .…”