Abstract 10806: The Role of Neuronal Nitric Oxide Synthase on the Vascular Hyporeactivity and Multiple Organ Failure Associated With Hemorrhagic Shock
Bibliographic record
Abstract
Introduction: Trauma can cause severe hemorrhage leading to a state of global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Several studies have shown the participation of nNOS-derived NO in the pathogenesis of the systemic inflammatory response and sepsis. However, the role of nNOS in HS is poorly understood. Hypothesis: The aim of this study is to investigate the role of nNOS-derived NO in the MOF associated with HS. Methods: Rats were subjected to HS under sodium thiopental anesthesia (120 mg/kg; i.p.). The blood pressure was reduced to 30 ± 2 mmHg for 90 min, followed by resuscitation with the shed blood. Rats were treated with 3 different nNOS inhbitors (S-methyl-L-thiocitrulline, ARL 17477 or 7 nitroindazol) or vehicle upon resuscitation. Four hours later, organ injury and dysfunction and the signaling events involved in the observed protective effects of nNOS inhibitors were investigated. Results: When compared to sham rats, HS resulted in a significant decrease in creatinine clearance and rises in serum creatinine, creatine kinase, lactate, aspartate and alanine aminotransferases, indicating the development of MOF. HS also resulted in vascular hyporeactivity to norepinephrine. Treatment of HS-rats with nNOS inhibitors protected animals against the MOF and vascular dysfunction induced by HS. When compared to HS control, analysis of kidney and liver tissue from HS rats treated with nNOS inhibitors revealed decreases in phosphorylation of IκB and p65 nuclear translocation of NF-κB, reduction in iNOS expression, NOx production and protein nitrosylation. nNOS inhibitors treatment also attenuated systemic pro-inflammatory cytokines formation. Conclusions: Our findings show that nNOS inhibition at the onset of resuscitation protects rats against the MOF and vascular dysfunction associated with HS thorough the attenuation of NF-κB activation and consequent reduction of NF-κB-dependent proteins (such as iNOS and pro-inflammatory cytokines), and thorough the attenuation of proteins nitrosylation by NO-derived species.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".