Abstract 2315: Markedly Enhanced Activity of Endothelin-1 in Transplant Coronary Arteriosclerosis
Bibliographic record
Abstract
Background: Coronary arteriosclerosis is the principal complication limiting long-term survival after heart transplantation. In humans, the mediators responsible for vascular proliferation and vasoconstriction typical of TCA are unknown. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen derived primarily from endothelial and mononuclear cells. We tested the hypothesis that ET-1’s biological activity is increased in TCA and that it may contribute to the pathogenesis and manifestations of TCA. We inhibited the ET A receptor by administering a specific antagonist BQ-123 into the coronary arteries in heart transplant recipients undergoing routine annual cardiac catheterization. We compared the coronary vasomotor responses to BQ-123 in subjects with angiographic evidence of TCA and subjects free of angiographic evidence of TCA. Methods: BQ-123 was infused into one proximal coronary artery (40nmol/min for 60min) of 18 subjects, age 18 –75, 6 +/− 4 years after transplantation. In each patient 3 coronary segments were studied in both the infused and in a non-infused control coronary artery (Total 108 segments). Changes from baseline in diameters of the infused arterial segments were compared to those of non-infused arterial segments at 15 minute intervals. Contribution of ET-1 to coronary constrictor tone was assessed by comparing vasodilation from BQ-123 infusion to dilation from intracoronary nitroglycerin (200μg bolus). Results: BQ-123 induced dilation in coronary arteries of transplanted patients (8.4% at 60 minutes, vs. −0.4% in noninfused arteries, p<0.001). Dilation was greater for arteries with TCA defined as angiographic diameter stenosis ≥15% (dilation 15.2% with TCA, n=10, vs. 0.6% without TCA, n=8, p=0.004). As compared to dilation from nitroglycerin indicative of overall vascular tone, ET-1 was responsible for 53.2% of vascular tone in TCA arteries but only 12.9% in arteries without TCA. Conclusions: The endogenous biological activity of ET-1 is markedly increased in humans with TCA compared to those without evidence of TCA. This supports a role for ET-1 in the pathogenesis of TCA and suggests that therapeutic targeting of ET-1 may slow the development and manifestations of TCA in cardiac transplant recipients.
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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".