Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction
Bibliographic record
Abstract
BACKGROUND: It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction. METHODS AND RESULTS: Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n=79) and age- and gender-matched patients with coronary artery disease and normal left ventricular function (n=79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; P<0.0001), symmetric dimethylarginine (P<0.0001), monomethylarginine (P=0.0003), nitrotyrosine (P<0.0001), and bromotyrosine (P<0.0001) and lower levels of arginine (P<0.0001), ratio of arginine to ornithine (P=0.03), and ratio of arginine to ornithine plus citrulline) (P=0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3; P=0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients. CONCLUSIONS: CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".