Effect of frusemide on transvascular fluid fluxes across the lung in exercising horses

REASONS FOR PERFORMING STUDY: Frusemide (Fru) is widely prescribed for management of racehorses experiencing EIPH. The effect of Fru in the lung appears to be a reduction in transcapillary pressures and inhibition of the erythrocyte anion exchange, which may lead to attenuation of transpulmonary fluid fluxes during exercise. HYPOTHESIS: Treatment with Fru will attenuate transpulmonary fluid fluxes in horses during high intensity exercise. METHODS: In a crossover study, 6 race-fit Standardbred horses were treated with 250 mg of Fru i.v. (FruTr) or placebo (Con) 4 h before exercise on a high speed treadmill until fatigue. Arterial and central mixed venous blood, as well as CO(2) elimination and O(2) uptake, were sampled. Volume changes across the lung and transvascular fluid fluxes were calculated from changes in haemoglobin, packed cell volume, plasma protein and cardiac output (Q). RESULTS: During exercise, Q increased in both Con and FruTr, with Q being significantly lower in FruTr (mean ± s.e. 301.8 ± 8.5 l/min at fatigue) compared to Con (336.5 ± 15.6 l/min) (P<0.01). At rest frusemide had no effect on erythrocyte (J(ER)) and transvascular (J(V-A)) fluid fluxes across the lung. Exercise had a significant effect on J(ER) and J(V-A) (P ≤ 0.02). During exercise, J(ER) (at fatigue 14.6 ± 2.3 l/min and 11.6 ± 2.2 l/min in Con and FruTr, respectively) and J(V-A) (at fatigue 14.9 ± 2.3 l/min and 12.0 ± 2.2 l/min in Con and FruTr, respectively) were not significantly different between Con and FruTr (P = 0.6 and P = 0.8 for J(ER) and J(V-A), respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Fru does not have a measurable effect on J(ER) and J(V-A). Cardiac output was reduced in FruTr, suggesting that there were also smaller changes in the capillary recruitment and transvascular transmural hydrostatic pressures; however, this did not effect J(V-A). Therefore, Fru at the dose of 250 mg does not appear to be an effective treatment for regulating pulmonary transvascular forces during exercise in horses.