317 The Cardio-Protective Effects of Doxycycline in a Swine Model of Neonatal Asphyxia
Bibliographic record
Abstract
Background Myocardial reoxygenation injury following asphyxia in neonates is common. Matrix metalloproteinase-2 activation is associated with myocardial ischemic-reperfusion injury and stunning. Previous in vitro, ex vivo, and small animal studies have demonstrated the cardio-protective qualities of doxycycline, a known inhibitor of matrix metalloproteinase-2, however, large animal models demonstrating this effect are lacking. We hypothesized that doxycycline would improve cardiac recovery and systemic hemodynamics in asphyxiated newborn piglets. Methods Piglets (1–5 days old) were acutely instrumented for continuous monitoring of heart rate, cardiac output [CO], mean systemic and pulmonary arterial pressures (SAP and PAP, respectively). After stabilization, 2hrs of normocapnic alveolar hypoxia (10–15% oxygen) was induced followed by 4hrs of normoxic reoxygenation (21% oxygen). Piglets were blindly randomized to receive either normal saline or doxycycline (3, 10, or 30mg/kg) intravenously 5 minutes into reoxygenation (n=7/group). Sham-operated piglets (n=5) received no hypoxia-reoxygenation. Results Asphyxiated piglets demonstrated acidosis (pH=7.04± [SD]0.08), hypotension (SAP=31±3mmHg), and cardiac dysfunction (CO= 58±8% of normoxic baseline). Doxycycline had dose-related improvements in CO and stroke volume (30 mg/kg: 86±8% and 79±15% of normoxic baseline vs. 65±7% and 50±13% in controls, respectively [both p<0.05]), with no significant change in heart rate compared to controls. Furthermore, SAP was higher and PAP/SAP ratio was lower than those of controls (p<0.05), with no difference in PAP. Conclusions In an established swine model of neonatal hypoxia-reoxygenation, post-resuscitation administration of intravenous doxycycline improves cardiac recovery with beneficial hemodynamic effects in systemic and pulmonary circulations. Funded by Canadian Institutes of Health Research (CIHR).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".