Dissociation of exercise-induced pulmonary hemorrhage and pulmonary artery pressure via nitric oxide synthase inhibition

During intense exercise, pulmonary capillary stress failure results in exercise-induced pulmonary hemorrhage (EIPH). To date, a principal focus has been the high pulmonary artery pressures (Ppa) manifest during high intensity exercise as one of the predominant mechanisms that elevates capillary transmural pressure resulting in rupture of the blood-gas barrier. However, it is possible that vascular pressures at other locations (e.g., venular) and extravascular pressures may also be important in the etiology of EIPH. To investigate further the relationship between EIPH and Ppa, five horses ran on an equine treadmill to volitional fatigue under control (CON) and nitric oxide synthase inhibition (L-NAME, 20 mg/kg, i.v.) conditions. Administration of L-NAME significantly increased EIPH (CON, 522.0 ± 453.8; L-NAME, 1178.7 ± 937.7 × 106 RBC/ml bronchoalveolar lavage fluid; p < 0.05) in all five horses despite reductions in Ppa and cardiac output () in four of the five horses. Within trials, Ppa was highly correlated with EIPH. However, across the range of Ppaʹs, the severity of EIPH was greater in the L-NAME run (p < 0.05). There was a significant positive relationship (r = 0.95, p < 0.05) between the change in maximal Ppa-to- ratio and the percentage change in EIPH between trials. These data suggest that events at other locations e.g., pulmonary venules and/or airways may be of great importance in regulating pulmonary capillary transmural pressure and inducing rupture of the blood-gas barrier.