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

During intense exercise, pulmonary capillary stress failure results in exer cise-induced pulmonary hemorrhage (EIPH). To date, a principal focus has be en the high pulmonary artery pressures (Ppa) manifest during high intensity exercise as one of the predominant mechanisms that elevates capillary tran smural 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 i nvestigate further the relationship between EIPH and Ppa, five horses ran o n an equine treadmill to volitional fatigue under control (CON) and nitric oxide synthase inhibition (L-NAME, 20 mg/kg, i.v.) conditions. Administrati on of L-NAME significantly increased EIPH (CON, 522.0 +/- 453.8; L-NAME, 11 78.7 +/- 937.7 x 10(6) RBC/ml bronchoalveolar lavage fluid; p < 0.05) in al l five horses despite reductions in Ppa and cardiac output ((Q)over dot) in four of the five horses. Within trials, Ppa was highly correlated with EIP H, However, across the range of Ppa's, 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-(Q)over dpt ratio a nd the percentage change in EIPH between trials. These data suggest that ev ents at other locations e.g., pulmonary venules and/or airways may be of gr eat importance in regulating pulmonary capillary transmural pressure and in ducing rupture of the blood-gas barrier.