Acetazolamide attenuates transvascular fluid flux in equine lungs during intense exercise
Bibliographic record
Abstract
Key points During high intensity exercise approximately 4% of the cardiac output leaves the pulmonary circulation into the interstitium. This fluid flux has been attributed to an increase in pulmonary transmural hydrostatic (Starling) forces. Fluid efflux from erythrocytes may account for a considerable fraction of fluid exiting the pulmonary circulation. Transcapillary erythrocyte volume changes are largely determined by the Jacobs–Stewart cycle, a series of intracellular and extracellular diffusion and chemical reaction events of carbon dioxide, water, bicarbonate, hydrogen ions and chloride that are initiated when blood is exposed to a gradient such as when blood enters and traverses systemic and pulmonary capillaries. We tested the hypothesis that the Jacobs–Stewart cycle contributes to pulmonary transvascular fluid fluxes during exercise by inhibiting red cell carbonic anhydrase, the activity of which is critical to rapid completion of the Jacobs–Stewart cycle during capillary transit. Our results indicate that during exercise in horses, transvascular fluid fluxes in the lung appear to be dependent on the Jacobs–Stewart cycle and much less dependent upon transmural hydrostatic (Starling) forces. It also appears that pulmonary circulation transvascular fluid fluxes are mediated by chloride and water egress from erythrocytes directly into the interstitium without transit through plasma, which is likely the result of functional apposition of the erythrocyte and vascular endothelial membranes occurring during capillary transit. Abstract During intense exercise in horses the transvascular fluid flux in the pulmonary circulation ( J v‐a ) represents 4% of cardiac output ( ). This fluid flux has been attributed to an increase in pulmonary transmural hydrostatic forces, increases in perfused microvascular surface area, and reversible alterations in capillary permeability under conditions of high flow and pressure. Erythrocyte fluid efflux, however, accounts for a significant fraction of J v‐a . In the lung the Jacobs–Stewart cycle occurs with diffusion of CO 2 into alveolar space with possible accompanying chloride (Cl − ) and water movement from the erythrocyte directly into the pulmonary interstitium. We hypothesised that inhibition of carbonic anhydrase in erythrocytes inhibits the Jacobs–Stewart cycle and attenuates J v‐a . Five horses were exercised on a treadmill until fatigue without (control) and with acetazolamide treatment (30 mg kg −1 30 min before exercise). Erythrocyte fluid efflux, plasma fluid flux across the lung and J v‐a were calculated using haemoglobin, haematocrit, plasma protein and Q. Fluid fluxes were used to calculate erythrocyte, plasma and whole blood Cl − fluxes across the lung. Cardiac output was not different between control and acetazolamide treatment. During exercise erythrocyte fluid efflux and J v‐a increased in control (9.3 ± 3.3 and 11.0 ± 4.4 l min −1 , respectively) and was higher than after acetazolamide treatment (3.8 ± 1.6 and 1.2 ± 1.2 l min −1 , respectively) ( P < 0.05). Plasma fluid flux did not change from rest in control and decreased after acetazolamide treatment (−4.5 ± 1.5 l min −1 ) ( P < 0.05). Erythrocyte Cl − flux increased during exercise in control and after acetazolamide treatment ( P < 0.05). During exercise plasma Cl − flux across the lung did not change in control; however, it increased with acetazolamide treatment ( P = 0.0001). During exercise whole blood Cl − flux increased across the lung in control ( P < 0.05) but not after acetazolamide treatment. The results indicate that J v‐a in the lung is dependent on the Jacobs–Stewart cycle and mostly independent of transmural hydrostatic forces. It also appears that J v‐a is mediated by Cl − and water egress from erythrocytes directly into the interstitium without transit through plasma.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".