A23 CIRCULATING PROPIONATE AND SPLANCHNIC VASODILATION IN CIRRHOSIS
Bibliographic record
Abstract
Splanchnic arterial vasodilation is at the center of the pathogenesis of cirrhosis complications since it contributes to portal hypertension and arterial hypotension. The mechanisms of vasodilation in cirrhosis are still not well understood which results in lack of targeted pharmacological therapies. Recently it has been shown in experimental animals that gut derived short chain fatty acids, in particular propionate, have vasoactive properties causing vasodilation. Our aim was to assess if propionate contributes to splanchnic vasodilation in cirrhosis. In 42 patients with cirrhosis (Child-Pugh A/B/C: 10/18/14) and portal hypertension we analysed plasma levels of propionate (LC-MS), HVPG and the transcriptome of liver biopsies. In sham-operated rats and rats with biliary cirrhosis (4 weeks of common bile duct ligation or CBDL), we assessed circulating propionate levels, and the hemodynamic effects of a continuous infusion of propionate (vs saline) on portal pressure (PP), mean arterial pressure (MAP) and superior mesenteric artery blood flow (SMABF, as a readout of splanchnic vasodilation). Cirrhosis patients showed increased circulating propionate above normal laboratory values that correlated with the degree of portal hypertension (p=0.004; Fig 1) and a downregulation of the metabolic pathway of propionate (FDR<0.000001). We then assessed in control (sham-operated) rats the effects of an infusion causing increase in propionate levels comparable to that observed in advanced cirrhosis. Propionate infusion caused an increase in SMABF (+64%, p<0.05) and hypotension (-12%, p<0.05),) without significantly modifying portal pressure (+6%, ns). Cirrhotic rats (CBDL) showed a 1.9 fold increase in propionate levels as compared to sham rats (p=0.047), that correlated with MAP (p<0.05), and a significant downregulation of liver propionate metabolic pathway (FDR<0.001). In cirrhotic rats propionate infusion induced a further worsening in cirrhosis hemodynamics, causing further decrease in MAP (-15%, p<0.05), increased SMABF (+48%, p<0.05) an increase in portal pressure (+14%, p<0.05). Propionate is increased in cirrhosis and correlates with the degree of portal hypertension. In rats an increase in circulating propionate induces hypotension, increases SMABF and, in cirrhotic rats, aggravates portal hypertension. Altogether this suggests that propionate contributes to the abnormal hemodynamics of advanced cirrhosis and might be an actionable target to improve arterial hypotension and portal hypertension in these patients. American Gastroenterological Association
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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 | 0.000 |
| 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) | 0.002 | 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".