Table 4.
Metabolite profiles before and after CPB.
| BALF Metabolites | Before CPB | After CPB | CPB Effect | Treatment Effect | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Control | HTK | O2 | Control | HTK | O2 | Time (After vs. Before) | Time * Group | HTK/Control | O2/Control | ||||||||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | FC | p-Value | p-Value | FC | p-Value | FC | p-Value | |
| Glycerol | 31.1 | 34 | 33.4 | 43 | 36.8 | 40 | 143.3 | 37 | 46.6 | 41 | 185.4 | 38 | - | - | 0.11 | 0.3 | 0.029 | 1.3 | 0.7 |
| Phosphocholine | 7.7 | 7 | 5.1 | 9 | 8.0 | 8 | 18.6 | 7 | 14.5 | 8 | 37.0 | 8 | 2 | <0.0001 | 0.7 | 0.9 | 0.6 | 2.2 | 0.3 |
| N-Acetyl-Glucosamine | 1.7 | 2 | 1.8 | 2 | 2.9 | 2 | 9.6 | 2 | 3.3 | 2 | 11.2 | 2 | - | - | 0.05 | 0.3 | 0.013 | 1.1 | 0.8 |
| Acetate | 9.0 | 1 | 9.6 | 2 | 7.6 | 1 | 13.7 | 1 | 11.4 | 2 | 13.9 | 1 | 1.6 | <0.0001 | 0.9 | 0.9 | 0.3 | 1 | 0.9 |
| Acetoacetic acid | 7.5 | 6 | 7.2 | 8 | 9.8 | 7 | 29.3 | 7 | 10.6 | 7 | 34.2 | 7 | - | - | 0.14 | 0.3 | 0.027 | 1.1 | 0.8 |
| Acetone | 5.6 | 2 | 4.6 | 3 | 6.2 | 2 | 15.8 | 2 | 10.5 | 2 | 10.7 | 2 | 2 | <0.0001 | 0.9 | 0.6 | 0.3 | 0.7 | 0.3 |
| Glucose | 8.8 | 9 | 12.1 | 12 | 11.1 | 11 | 83.4 | 10 | 66.3 | 11 | 71.9 | 11 | 10 | <0.0001 | 1.0 | 0.9 | 0.7 | 0.9 | 0.7 |
| Lactate | 70.6 | 19 | 73.8 | 24 | 83.2 | 22 | 224.0 | 21 | 178.0 | 23 | 228.1 | 21 | 2.9 | <0.0001 | 0.4 | 0.8 | 0.2 | 1 | 0.9 |
| Pyruvate | 0.9 | 1 | 1.4 | 1 | 1.9 | 1 | 7.6 | 1 | 7.3 | 1 | 7.5 | 1 | 6.2 | <0.0001 | 1.0 | 1 | 1 | 1 | 0.9 |
| Alanine | 1.1 | 2 | 2.3 | 3 | 2.8 | 3 | 11.0 | 3 | 22.1 | 3 | 10.9 | 3 | 7.9 | <0.0001 | 0.05 | 1.8 | 0.13 | 1 | 1 |
| Citrate | 1.9 | 1 | 3.8 | 1 | 4.6 | 1 | 9.6 | 1 | 7.3 | 1 | 9.7 | 1 | 2.4 | <0.0001 | 0.7 | 0.8 | 0.3 | 1.1 | 0.8 |
| 2-Ketoglutarate | 12.3 | 5 | 14.0 | 6 | 13.9 | 6 | 33.9 | 6 | 16.0 | 6 | 38.1 | 6 | - | - | 0.02 | 0.5 | 0.005 | 1.1 | 0.8 |
| Succinate | 4.0 | 3 | 5.1 | 4 | 5.5 | 3 | 16.9 | 3 | 7.5 | 3 | 19.5 | 3 | - | - | 0.08 | 0.4 | 0.025 | 1.1 | 0.8 |
| Creatine | 0.4 | 1 | 0.7 | 1 | 0.6 | 1 | 3.0 | 1 | 3.0 | 1 | 3.6 | 1 | 5.8 | <0.0001 | 0.7 | 1 | 1 | 1.2 | 0.7 |
| Creatinine | 2.3 | 2 | 1.8 | 2 | 3.5 | 2 | 18.8 | 2 | 14.9 | 2 | 15.5 | 2 | 6.5 | <0.0001 | 0.8 | 0.8 | 0.5 | 0.8 | 0.5 |
| Isoleucine | 1.1 | 1 | 1.4 | 1 | 0.8 | 1 | 3.9 | 1 | 3.3 | 1 | 2.3 | 1 | 2.3 | 0.0004 | 0.3 | 0.9 | 0.4 | 0.7 | 0.2 |
| Valine | 1.6 | 1 | 2.1 | 1 | 1.9 | 1 | 5.1 | 1 | 5.1 | 1 | 3.5 | 1 | 2.2 | 0.0001 | 0.07 | 0.9 | 0.7 | 0.7 | 0.2 |
| Urea | 8.8 | 6 | 4.3 | 8 | 7.2 | 7 | 39.5 | 7 | 44.2 | 7 | 47.2 | 7 | 19.9 | <0.0001 | 0.6 | 1.4 | 0.3 | 1.2 | 0.4 |
| Arginine | 2.7 | 11 | 2.2 | 14 | 2.8 | 13 | 74.6 | 12 | 50.2 | 14 | 69.3 | 13 | 28.1 | <0.0001 | 0.5 | 0.7 | 0.5 | 1 | 0.9 |
| Methionine | 0.2 | 3 | 0.0 | 3 | 0.0 | 3 | 13.2 | 3 | 12.5 | 3 | 12.7 | 3 | 88.6 | <0.0001 | 1.0 | 1.1 | 0.8 | 1 | 1 |
| Dimethylamine | 0.4 | 0 | 0.6 | 0 | 0.3 | 0 | 1.7 | 0 | 2.0 | 0 | 1.1 | 0 | 3.3 | <0.0001 | 0.14 | 1.2 | 0.5 | 0.6 | 0.2 |
| Dimethyl sulfone | 3.3 | 1 | 3.9 | 1 | 4.1 | 1 | 6.0 | 1 | 11.7 | 1 | 5.4 | 1 | - | - | 0.004 | 2.1 | 0.004 | 0.9 | 0.8 |
| Histidine | 0.1 | 29 | 0.0 | 36 | 0.5 | 33 | 3.0 | 31 | 250.8 | 35 | 3.2 | 32 | - | - | <0.0001 | 67.8 | 0.0002 | 1.1 | 0.9 |
| Phenylalanine | 22.8 | 4 | 18.2 | 6 | 23.7 | 5 | 36.0 | 5 | 26.8 | 5 | 34.1 | 5 | 2 | 0.01 | 0.3 | 0.7 | 0.14 | 0.9 | 0.5 |
| Inosine | 4.5 | 1 | 4.2 | 1 | 3.4 | 1 | 5.1 | 1 | 6.2 | 1 | 4.9 | 1 | 1.3 | 0.008 | 0.5 | 1.2 | 0.4 | 0.9 | 0.5 |
| Hypoxanthine | 4.6 | 1 | 4.4 | 2 | 4.4 | 2 | 9.0 | 1 | 10.4 | 2 | 9.6 | 1 | 3.3 | 0.0002 | 0.9 | 1.1 | 0.7 | 1 | 1 |
| Mannitol | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 687.7 | 69 | 675.4 | 76 | 624.8 | 71 | 90 | <0.0001 | 0.9 | 1 | 1 | 0.9 | 0.6 |
Because several metabolites were without any signal in samples collected before CPB, their mean concentrations were below the limit of NMR detection. Mean fold change (FC) were calculated as the ratio between the metabolites measured (1) before and after CPB (CPB effect), and (2) by comparing the standard regimen versus oxygenated blood group and the standard CPB regimen versus HTK group after CPB (Treatment effect). “-” these metabolites have been found different among groups post-CPB, and hence, FC and p-values for the before and after analysis are not provided to avoid misinterpretation. To assess the effect of CPB on BALF metabolites the pair t-test or its corresponding non-parametric test was applied, while for the effect of treatment received the factorial two-way ANOVA (Time-Group interactions) and its corresponding Tuckey’s post-hoc test for group comparison was used (HTK/Control; O2/Control). A two-tailed p-value ≤ 0.05 was considered significant.