Transvascular fluid dynamics in the pulmonary vasculature in horses at rest and during exercise

Maximal exercise results in a marked increase in cardiac output (Q) with consequent adaptations in pulmonary macro- and microvasculature. These adaptations change pulmonary hemodynamics and increase fluid and solute movement between the pulmonary circulation and the pulmonary interstitium (across the lung). The purpose of this study was to determine pulmonary circulation transvascular fluid fluxes in a quantitative manner during exercise in horses. This was determined during exercise at 80% VO2max on a high-speed treadmill until fatigue without any medication, with acetazolamide (Acz) treatment, and with furosemide (Fur) treatment. Acetazolamide, a carbonic anhydrase (CA) inhibitor, has several effects on pulmonary vasculature and erythrocytes, which influence pulmonary circulation transvascular fluid fluxes and electrolyte changes across the lung. These mechanisms are expressed through its ability to reduce vascular smooth muscle tone and contractility, and to attenuate hydration/dehydration of CO2 via the CA, Jacobs-Stewart cycle and chloride shift (Hamburger shift) inhibition. Furosemide causes diuresis. The consequence of diuresis is a decrease in plasma volume, right ventricular preload, and Q, which results in reduction in transmural hydrostatic pressures in pulmonary vasculature. Reduction of transmural hydrostatic forces is the mechanism by which Fur is believed to attenuate exercise induced pulmonary hemorrhage. Furosemide has also a dilatory effect on the pulmonary vasculature, and it may affect the chloride shift across the erythrocyte membrane. Resting, exercise, and recovery arterial and mixed venous blood were sampled from race fit standarbred horses. Blood (BV) and erythrocyte volume (EV) changes across the lung were calculated from changes in plasma protein, hemoglobin and hematocrit. Cardiac output was calculated using Fick equation. Fluid flux across the lung was quantified based on changes in BV and EV across the lung. Integrative physicochemical systems approach was used to describe acid base changes across the lung. The overall findings of these studies showed that approximately 12 L/min or 4 % of Q moves from the pulmonary circulation into the pulmonary interstitium during exertion in horses. This volume, which left the pulmonary circulation, was derived primarily from the reduction of erythrocytes’ volume across the lung. Acetazolamide attenuated transvascular fluid fluxes in the pulmonary circulation through attenuation of the erythrocyte volume changes. It did not change Q. Furosemide did not affect erythrocyte volume changes and transvascular fluid fluxes in the pulmonary circulation, but reduced Q. Cardiac output during exercise is indicative of pulmonary capillary recruitment and/or dilatation coupled with the increase in the pulmonary surface area. From the results of our studies we conclude that pulmonary circulation transvascular fluid fluxes are regulated by erythrocyte volume regulation. Hydrostatic transmural gradients across the pulmonary vasculature have a minor effect on pulmonary circulation transvascular fluid fluxes during exercise in horses.