Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage

Abstract

Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions of the capillary endothelial and alveolar epithelial layers, extensive collections of red blood cells in the alveolar wall interstitium, proteinaceous fluid and red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen. The appearances were consistent with the ultrastructural changes we have previously described in rabbit lungs at high capillary transmural pressures. Actual breaks in the endothelium and epithelium were rather difficult to find, and they were frequently associated with platelets and leukocytes that appeared to be plugging the breaks. The paucity of breaks was ascribed to their reversibility when the pressure was lowered and to the fact that 60-70 min elapsed between the gallop and the beginning of lung fixation. Capillary wall stress was calculated from pulmonary vascular pressures measured in a companion study (Jones et al. FASEB J. 6: A2020, 1992) and from measurements of the thickness of the blood-gas barrier and the radius of curvature of the capillaries. The value was as high as 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2), which exceeds the breaking stress of most soft tissues. We conclude that stress failure of pulmonary capillaries is the mechanism of EIPH.

Nitric oxide and exercise in the horse.

“…The exercise-induced increase in PAP in the horse (>80 mmHg; Erickson, Erickson & Coffman, 1990;Manohar, 1994), is significantly higher than in other species, including man (approximately 30 mmHg; West et al 1993). The incidence of exercise-induced pulmonary haemorrhage (EIPH), a major problem in the racehorse (West et al 1993;Manohar, 1995), has been associated with a sudden and marked increase in PAP (Erickson et al 1990;Manohar, 1994;West & Mathieu-Costello, 1995). Little is known horse, although Manohar (1995) reported a reduction in pulmonary vascular pressures in the resting horse after administration of glyceryl trinitrate, a NO donor (Moncada et al 1991 (Butler et al 1993).…”

“…Persson et al (1993) Bauer et al 1994). This species difference may be expected if, indeed, NO contributes to the regulation of pulmonary vascular tone in the horse because pulmonary vascular pressures in this species are significantly higher during exercise than other species, including man (Erickson et al 1990;West et al 1993;West & Mathieu-Costello, 1995 Nitric oxide and exercise in the horse Bauer et al (1994) bronchiectasis and sinus inversus, has been associated with a deficiency of NO in the paranasal sinuses (Lundberg et al 1995). Furthermore, nitrate-forming bacteria in the upper airways could also contribute to exhaled NO (Gerlach et al 1994 Several studies have suggested that NO in exhaled air could originate from the lower airways, particularly the terminal and respiratory bronchioles (Gustafsson et al 1991;Persson et al 1993;Cremona et al 1995).…”

“…Furthermore, in athletic species the lung is adapted to high-intensity exercise by an eightfold increase in pulmonary vascular flow and a thin pulmonary blood-gas barrier to permit rapid gas exchange (Wagner et al 1989;West & Mathieu-Costello, 1995). The superior o02,max of the horse requires a comparatively higher cardiac output and subsequently, a higher PAP than other species, which will also predispose the horse to stress failure and subsequent rupture of pulmonary capillaries during near-maximal exercise (Wagner et al 1989;West et al 1993;West & Mathieu-Costello, 1995). Stress failure of pulmonary capillaries, resulting from excessive pulmonary vascular pressure during high-intensity exercise has been implicated in the pathogenesis of EIPH (West et al 1993;West & Mathieu-Costello, 1995), a major problem in the horse during racing (Erickson et al 1990; West et al 1993).…”

“…The superior o02,max of the horse requires a comparatively higher cardiac output and subsequently, a higher PAP than other species, which will also predispose the horse to stress failure and subsequent rupture of pulmonary capillaries during near-maximal exercise (Wagner et al 1989;West et al 1993;West & Mathieu-Costello, 1995). Stress failure of pulmonary capillaries, resulting from excessive pulmonary vascular pressure during high-intensity exercise has been implicated in the pathogenesis of EIPH (West et al 1993;West & Mathieu-Costello, 1995), a major problem in the horse during racing (Erickson et al 1990; West et al 1993). The severity of pulmonary capillary damage directly correlates with increasing PAP (West & Mathieu-Costello, 1995) and blood volume (Wagner et al 1989).…”

Exercise-induced pulmonary haemorrhage in horses – review

“…The fact that EIPH occurs after high-intensity exercise and prolonged low-intensity exercise suggests that this problem is due to extreme mechanical stresses on the tissue and pulmonary vessels during exercise (Art and Lekeux 1994). However, West et al (1993) observed episodes of EIPH in horses just after walking and trotting. There is a trend related to age, where older horses have shown increased susceptibility to episodes of EIPH (Lapointe et al 1994).…”