Pharmacokinetic Characterization of Intravenous Cyclosporine Treatment for Cardioprotection During Resuscitation of Asphyxiated Newborn Piglets
Bibliographic record
Abstract
OBJECTIVES: Cyclosporine treatment, as a single intravenous bolus, during resuscitation has been shown to attenuate myocardial injury in asphyxiated newborn piglets. However, the pharmacokinetics of cyclosporine treatment for cardioprotection in newborns has not been studied. We aimed to assess the pharmacokinetics of a single intravenous cyclosporine treatment during resuscitation of asphyxiated newborn piglets and compare these parameters with healthy newborn piglets. DESIGN: Newborn piglets were acutely instrumented and normocapnic alveolar hypoxia was induced for 2 hours followed by 4 hours of reoxygenation. Piglets were block-randomized to receive a single intravenous bolus of cyclosporine (2.5-25 mg/kg) (n = 8 per group). Eight piglets underwent no hypoxia-reoxygenation and received 10 mg/kg cyclosporine at the corresponding time point. Plasma cyclosporine and troponin concentrations during reoxygenation period were determined by high-pressure liquid chromatography and enzyme-linked immunosorbent assay, respectively. Noncompartmental methods were used to calculate the pharmacokinetic parameters. Cyclosporine concentrations and pharmacokinetic parameters were analyzed by one-way analysis of variance. SETTING: University animal laboratory. SUBJECTS: Piglets (1-4 days old, weighing 1.4-2.5 kg). INTERVENTIONS: Intravenous cyclosporine (2.5, 10, or 25 mg/kg) given during resuscitation. MEASUREMENTS AND MAIN RESULTS: In the hypoxic-reoxygenated piglets, the plasma AUC(0-4 hrs) and C(max) of cyclosporine at reoxygenation were in the following rank order: 25 > 10 > 2.5 mg/kg treatment (p < 0.001 between groups, analysis of variance). Plasma AUC(0-4 hrs) and C(max) in piglets treated with cyclosporine at 25 mg/kg was associated with increased plasma troponin levels, a marker of myocardial injury, relative to piglets treated with 2.5 and 10 mg/kg. Asphyxiated newborn piglets had higher clearance and lower AUC(0-∞), but similar AUC(0-4 hrs), steady-state volume of distribution, and mean residence time compared with those of healthy newborn piglets. CONCLUSIONS: This is the first study to demonstrate the pharmacokinetics of intravenous cyclosporine treatment during resuscitation of asphyxiated newborn piglets, which did not appear to different from that of healthy piglets.
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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 | 0.001 |
| 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".