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Abstract

Introduction: CNS and renal dysfunction in cardiopulmonary bypass (CPB) is reported to be as high as 50% with unclear underlying mechanisms. Hemolysis from CPB causes the release of free hemoglobin (fHb) which is a likely participant. Methods: Children (n=21, 4.6m [3m-17y]) undergoing CPB were prospectively enrolled. Forehead near infrared spectroscopy (NIRS) probes were placed. Plasma and urine were collected at CPB start (S), end (E), 2h and 24h reperfusion (R). Plasma was assayed for fHb (colorimetry), LDH, and ascorbate (fluorescence). The first 10 patients were also assayed for plasma NO consumption (chemiluminescence) and brain and renal injury markers (myelin basic protein [MBP] and neutrophil gelatinase-associated lipocalin [NGAL], ELISA). Urine was assayed for inosine/adenosine ratio (I/A, LC-MS). Data are shown as mean±SEM and analyzed by RM ANOVA and Pearson or Spearman correlations. All reported values are statistically significant (p<.05). Results: FHb (mg/dL) increased on CPB (S 9 ± 2, E 85 ± 10) and was positively correlated with CPB duration (r=0.63), LDH (r=0.75), MBP (rs=0.3), NGAL (rs=0.4), NO consumption (rs=0.9), and I/A (rs=0.4). It was inversely correlated with NIRS (rs =-0.3) and ascorbate (rs=-0.7). NIRS (%) decreased during CPB (S 70 ± 4, CPB 59 ± 3). Serum creatinine increased in 76% of patients; 48% and 10% met criteria for risk and injury by pRIFLE. MBP (ng/mL) and NGAL (pg/mL) rose during CPB ([S 0.3 ± 0.1, 2hR 0.4 ± 0.1] and [S 146 ± 21, E 299 ± 42], respectively). NO consumption (μM) and I/A ratios increased ([S 7 ± 2, E 32 ± 6] and [S 0.9 ± 0.2, 2hR 2.6 ± 0.8], respectively) while ascorbate (μM) decreased (S 43 ± 5, E 22 ± 4). All reported values are significant (p<.05). Conclusions: Hemolysis-related increases in fHb and its correlations with markers of organ injury suggest blood flow compromise and contribution to organ dysfunction. fHb may mediate several mechanisms including the reaction with NO and the peroxidase activity of fHb, which consumes NO and ascorbate. Adenosine deficiency may also result from adenosine deaminase release during hemolysis. These represent potential targets for therapies to mitigate CPB related injury. Support:T32HD040686;A Thompson Scholarship;VMI(UL1TR000005)