Current understanding of EIPH pathogenesis

Exercise-induced pulmonary hemorrhage (EIPH) is common in racehorses. It is a consequence of the physiological responses to exercise and is unaccompanied by signs of distress and other pulmonary disease.[1] This talk summarizes the physiological changes in breathing and circulation that lead to capillary rupture and EIPH. To deliver the oxygen necessary for running, both alveolar ventilation and cardiac output increase, and, as a consequence, pulmonary capillary transmural pressure (Pcap- tm) exceeds the minimum of 75 mm Hg necessary for capillary stress failure so that blood enters the air spaces.[2] The two determinants of Pcap-tm are pulmonary capillary (Pcap) and alveolar pressure (Palv). To supply the increase in both tidal volume and inspiratory air flow rate during exercise, Palv may decrease to values as low as minus 60 mm Hg during inhalation.[3] Concurrently Pcap may reach 75 mm Hg or greater so that Pcap-tm is 150 mm Hg. Pcap is a function of pulmonary arterial (Ppa) and left atrial (Pla) pressures, cardiac output (CO) and its regional distribution in the lung. Blood flow is greatest in the caudo-dorsal lung, which also is the site of EIPH and its associated lesions. During racing, heart rate increases to 220 bpm. CO, which is 30 L/min at rest, increases 10- fold or more. Even though the pulmonary circulation dilates to accommodate the increased blood flow, Ppa still increases from 25 to 90-plus mm Hg, in part because Pla increases from 10 to almost 50 mmHg. [4] The high Pla assists ventricular filling with about 1.75L of blood during the very short ventricular diastole (0.14 s). The elevated Pla also is, however, most likely the cause of pulmonary small vein remodeling, which by obstructing venous outflow, further increases Pcap. Small vein remodeling is a key EIPH lesion and always accompanies hemosiderin accumulations and interstitial fibrosis.[5] Such lesions are typical of other conditions associated with elevated Pla. Venous remodeling of caudo-dorsal small veins is not restricted to horses with career-ending EIPH because, in comparisons of the mechanical properties of small arteries and veins from raced and non-raced horses, racing is associated with preferential stiffening of caudo-dorsal small veins.[6] Because of the likely key role of left atrial pressure in EIPH, it would be of interest to determine if individual variations among horses in Pla are correlated with the magnitude of pulmonary hemorrhage.