Welcome to the all-new Vetlearn

  • What’s new on Vetlearn?
  • The latest issues of Compendium and
    Veterinary Technician
  • New CE articles for veterinarians and technicians
  • Expert advice on practice management
  • Care guides on more than 400 subjects
    to give to your clients
  • And more!

To access Vetlearn, you must first sign in or register.

registernow

Become a Member

Compendium April 2011 (Vol 33, No 4)

Exercise-Induced Pulmonary Hemorrhage in Horses: The Role of Pulmonary Veins

by Frederik Derksen, DVM, PhD, DACVIM, Kurt J. Williams, DVM, PhD, DACVP, Alice Stack, MVB

    CETEST This course is approved for 3.0 CE credits

    Start Test

    Abstract

    While airway endoscopy and bronchoalveolar lavage are the methods of choice for diagnosing exercise-induced pulmonary hemorrhage (EIPH), these techniques do not allow accurate evaluation of the severity of bleeding. EIPH pathology is characterized by occlusive remodeling of pulmonary veins. Affected veins have large collagen deposits in their walls, which reduces their lumens. In the caudodorsal regions, pulmonary vein wall remodeling is associated with hemosiderin accumulation, bronchial circulation angiogenesis, and fibrosis of the alveolar interstitium, bronchovascular bundle, septa, and pleura. During exercise, venous occlusion increases regional pulmonary capillary pressure, likely causing capillary rupture and resulting in bleeding.

    The relationship between strenuous exercise and bleeding in horses has been recognized since at least the early 18th century. For example, the brother of Flying Childers, one of the founding stallions of the Thoroughbred breed, was given the ignominious name Bleeding Childers because of his propensity to bleed from the nose after exercise. The source of this blood remained a mystery until the 20th century, when Cook1 used a rigid endoscope to inspect the nasal airways for the source of blood. Partly because Cook did not find the source of blood in the nose, he hypothesized that epistaxis after exercise originated in the lungs.1

    By 1981, the flexible fiberoptic endoscope had become more widely available. Using this new technology, Pascoe et al2 reported that blood was present in the tracheas of 44% of Thoroughbreds after racing. From this study, it was concluded that the bleeding originated in the lungs, and the term exercise-induced pulmonary hemorrhage (EIPH) was coined. Subsequent studies have confirmed the prevalence of EIPH in Thoroughbreds after racing to be 47% to 75%.3,4

    Key Points

    • EIPH is typically associated with racing Thoroughbreds and Standardbreds; however, this performance-limiting condition may affect any strenuously exercised horse.
    • Accepted methods for diagnosing EIPH (i.e., tracheal endoscopy, bronchoalveolar lavage) may not accurately indicate the severity of bleeding.When reviewing the literature on this subject, readers should be mindful of this limitation and should not be surprised by variability in study results.
    • Regional remodeling of pulmonary veins is an important lesion in EIPH. Affected veins have large collagen deposits in their walls, which thickens the walls and reduces the venous lumen (venous occlusion).
    • Multiple examinations after exercise are required to fully determine the status of individual horses with EIPH.

    When racehorses were examined after running two races, the prevalence of EIPH after at least one race increased5; when Standardbreds or Thoroughbreds were examined after running three races, 100% of these horses had blood in the trachea at least once.6 Bronchoalveolar lavage (BAL) can be used to demonstrate that 90% of racehorses that perform intense exercise experience episodes of pulmonary hemorrhage.7 EIPH is not restricted to Standardbreds and Thoroughbreds; it also occurs in other breeds that perform strenuously, such as racing Quarter horses,8 polo ponies,9 and 3-day event horses.10 Most studies4,11,12 have indicated that the prevalence of EIPH increases with a horse’s age. One study suggested that time in training, rather than age, correlated with EIPH.13 The increased incidence of EIPH associated with time in training suggests that repeated episodes of hemorrhage result in progressive pulmonary damage.

    Diagnosis

    Examination of the upper airway and trachea using a fiberoptic endoscope has been the method of choice for diagnosing EIPH. In general, the upper and lower respiratory tracts of horses are endoscopically evaluated within 2 hours after exercise.4,12 Investigators have attempted to quantify the degree of hemorrhage based on the amount of blood in the trachea, which can range from a few flecks of blood to multiple coalescing streams of blood covering more than 90% of the tracheal wall.14 This scoring system is useful, but it is not ideal because the amount of blood in the trachea after racing varies in individual horses. Thus, a single examination of an individual horse after exercise may be misleading because a horse may seem unaffected by EIPH after a specific race but may have severe EIPH after subsequent races.6 However, it is possible that the amount of bleeding in the lungs is consistent from race to race but that the blood is not mobilized consistently into the trachea. Thus, multiple examinations after exercise are required to fully determine the status of individual horses with EIPH. Multiple examinations are also useful because horses with severe EIPH bleed more frequently.5

    Other studies have used BAL to diagnose EIPH. This technique is quantitative and more sensitive than tracheal endoscopy because red blood cells (RBCs) can be detected in BAL fluid without endoscopic evidence of blood in the trachea.15 However, this method only samples a small portion of one lung, and the location of bleeding may be remote from the site sampled. The location of bleeding probably also varies in individual horses and from race to race. Therefore, it is no surprise that the RBC counts in BAL fluid collected from the right and left lungs of individual horses differ significantly.16 Further, the technique is too invasive for routine clinical use. A survey of racehorses in training found that 73% of BAL samples had evidence of free RBCs and 90% of samples had hemosiderophages.7 Hemosiderophages offer evidence of EIPH and can be detected in the tracheal wash fluid of virtually all vigorously exercised horses that are examined repeatedly.17 The presence of hemosiderophages in BAL fluid does not accurately predict when hemorrhage occurred, as hemosiderophages are cleared slowly and found in BAL fluid of horses for at least 5 weeks after exercise.15

    Effects on Pulmonary Function and Performance

    Changes in pulmonary function caused by EIPH can be demonstrated by ventilation and perfusion imaging of lung fields using radioactive nucleotides. In a study of five horses with confirmed EIPH, radiographic opacities in the caudodorsal lung field correlated with regions of ventilation/perfusion mismatch.18 Therefore, it is not surprising that EIPH affects performance. In a large study of Thoroughbreds, Hinchcliff et al12 documented that even modest EIPH affects performance. Horses were graded on a scale from 0 (unaffected) to 4 (most severely affected). There was a significant association between the presence of grade ≥2 EIPH and (1) lower odds of winning or finishing in the first three positions, (2) finishing a longer distance behind the winner, and (3) a lower likelihood of being in the 90th percentile or higher for race earnings.

    Pulmonary Pathology

    Studies of the pathology of equine EIPH, while not numerous, have been important in the evolution of understanding the pathogenesis of this disease. The first extensive investigation of the gross and histologic features of EIPH was performed more than 20 years ago.19 The investigators described the clinical features of 26 horses with EIPH and the pathologic lesions of 19 of them. The reported gross lesions included bilateral, symmetric dark discoloration of the pleura of the caudodorsal lung (FIGURE 1) , with the underlying lungtissue described as firmer than normal lung tissue. Histologically, the primary findings were described as scattered bronchiolitis, hemosiderophage accumulation, fibrosis, and angiogenesis.19 Based on this study, it was suggested that EIPH results from bronchiolitis, with the bleeding arising from bronchial circulation proliferation in response to chronic airway inflammation.20 In a 1993 study on the ultrastructure of alveoli in horses with EIPH, West et al21 detected tears in the alveolar capillary wall. This study involving three horses has been the basis for the most widely mentioned hypothesis for the pathogenesis of EIPH, namely that exercise-induced alveolar capillary hypertension results in capillary wall stress failure. However, the reported histologic lesions of EIPH suggest that the pathogenesis is more complex than simple capillary wall tearing.

    The Role of Pulmonary Veins

    In another article,22 we (Williams and Derksen) confirmed the caudodorsal lung’s predilection for lesion development in EIPH. In the study, we identified a constellation of histologic findings (i.e., hemosiderin accumulation, interstitial fibrosis, pleural and septal fibrosis, foci of angiogenesis that occur together with a previously unrecognized pulmonary venous lesion) that may have important implications in the pathogenesis of EIPH. The most dramatic of these venous changes is regional veno-occlusive remodeling of small branches of intrapulmonary veins (FIGURE 2) . Affected veins have large collagen deposits in their walls, causing thickening of the vein wall and reduction of the venous lumen. In the caudodorsal regions, where lesions are more severe, pulmonary vein wall remodeling is associated with hemosiderin accumulation, bronchial vasculature angiogenesis, and fibrosis of the alveolar interstitium, bronchovascular bundle, septa, and pleura. The lesions in these regions are far more severe than previously reported. While collagen accumulation around pulmonary veins can occur alone, significant hemosiderin accumulation, angiogenesis, and fibrosis of pulmonary structures do not occur without coincident venous remodeling. The spatial association between hemosiderin accumulation and characteristic lesions of EIPH suggests that bleeding during exercise arises from foci centered around venous remodeling. All of the studies of the pathology of EIPH involved severely affected horses, and results should be cautiously extrapolated to mildly affected horses.

    Venous Hypertension and Vein Wall Remodeling

    What could cause such marked venous remodeling in horses with EIPH? Veins are thin-walled vessels designed to function as low-pressure, high-volume conduits for blood flow. Experimentally, high venous pressure, even for short periods of time, elicits remodeling of the vessel wall.23 This remodeling is important for preventing catastrophic rupture. Racehorses train and race frequently, and, in strenuously exercising horses, pulmonary veins are subjected to pressures as high as 80 mm Hg.24 (In horses, normal venous pressure at rest is about 20 mm Hg; in other species, the increase in pulmonary vascular pressure with exercise is much smaller—often less than half that in horses.) These data suggest that repeated bouts of high pulmonary venous pressure in strenuously exercising horses might be responsible for the vein wall fibrosis and remodeling observed in these studies.

    FIGURE 3  presents a diagram of our proposed pathogenesis of EIPH. First, high-intensity exercise results in high pulmonary vascular pressure. In exercising horses, pulmonary blood flow is preferentially distributed to the caudodorsal lung regions25; therefore, it is possible that pulmonary venous pressure is particularly high in these regions. Repeated bouts of high vascular pressure result in pulmonary vein wall remodeling, including collagen deposition in the vein wall. This remodeling causes narrowing of the venous lumen as well as regional venous occlusion. During exercise, venous occlusion results in regionally severe increases in pulmonary capillary pressure, capillary rupture, and bleeding. The bleeding causes deposition of blood in the alveoli and pulmonary interstitium, a local influx of macrophages, and conversion of RBCs to hemosiderin by the macrophages. Hemosiderin accumulation in tissues, rather than only being present in the airway,26 causes fibrosis in the interstitium, septa, and pleura. This also results in bronchial vasculature angiogenesis, which may exacerbate bleeding during exercise. Lastly, regional venous occlusion in the caudodorsal region results in diversion of blood flow to other lung regions and extension of the EIPH lesion in a cranial direction.

    If this proposed pathogenesis is correct, it could greatly affect how EIPH is managed, helping to reduce its incidence or even preventing it altogether. For example, confirming a pivotal role for pulmonary vein remodeling in the pathogenesis of EIPH should lead to new research on venodilators. Preliminary data from another laboratory suggest that venodilators significantly reduce the severity of EIPH.27 A better understanding of the pathobiology of EIPH may help researchers devise strategies to reduce the associated severity of bleeding and chronic pulmonary effects.

    Treatment

    When evaluating the effectiveness of a treatment for EIPH, clinicians should be mindful of the limitations of the diagnostic techniques (i.e., tracheal endoscopy, BAL) and should not be surprised by variability in study results.

    In North America, furosemide is the most popular drug for treating EIPH. Several studies have demonstrated that furosemide decreases the amount of bleeding.28,29 However, furosemide does not stop bleeding, and, in many treated horses, blood is still observed in the trachea after high-intensity exercise.6 The drug decreases pulmonary vascular pressure (probably partly by decreasing plasma volume and partly by venodilation) in horses exercising on a high-speed treadmill, so this is probably the mechanism by which the drug exerts its effect.24

    In addition, furosemide likely enhances the performance of horses independent of its effect on pulmonary hemorrhage. The drug’s diuretic effect causes horses to lose a significant volume of water, weigh less, and therefore race faster.30

    A nasal dilator device (nasal strip) has become popular. The nasal strip dilates the nose and reduces upper airway resistance.31 The nasal strip also diminishes EIPH,28 probably by reducing inspiratory pressure in the alveoli. Reduction of this pressure during exercise reduces the pressure difference across the pulmonary capillary wall (pulmonary capillary pressure minus alveolar pressure); therefore, the capillaries are less likely to rupture. Because the device has no adverse effects, it is likely to prove useful in a multipronged approach to preventing EIPH.  BOX 1 summarizes the proposed treatments for EIPH.3,16,27,28,32–41

    In the future, therapeutic regimens may significantly decrease vascular pressure in exercising horses, particularly in pulmonary veins. This would reduce inward remodeling and scarring of pulmonary veins and reduce venous obstruction. Further, pharmacologic intervention may ameliorate the interstitial fibrosis characteristic of the EIPH lesion.

    Downloadable PDF

    1. Cook WR. Epistaxis in the racehorse. Equine Vet J 1974;6:45-58.

    2. Pascoe JR, Ferraro GL, Cannon JH, et al. Exercise-induced pulmonary hemorrhage in racing thoroughbreds: a preliminary study. Am J Vet Res 1981;42:703-707.

    3. Mason DK, Collins EA, Watkins KL. Effect of bedding on the incidence of exercise induced pulmonary haemorrhage in racehorses in Hong Kong. Vet Rec 1984;115:268-269.

    4. Raphel CF, Soma LR. Exercise-induced pulmonary hemorrhage in Thoroughbreds after racing and breezing. Am J Vet Res 1982;43:1123-1127.

    5. Lapointe JM, Vrins A, McCarvill E. A survey of exercise-induced pulmonary haemorrhage in Quebec Standardbred racehorses. Equine Vet J 1994;26:482-485.

    6. Birks EK, Shuler KM, Soma LR, et al. EIPH: postrace endoscopic evaluation of Standardbreds and Thoroughbreds. Equine Vet J Suppl 2002;34:375-378.

    7. McKane SA, Canfield PJ, Rose RJ. Equine bronchoalveolar lavage cytology: survey of Thoroughbred racehorses in training. Aust Vet J 1993;70:401-404.

    8. Hillidge CJ, Whitlock TW. Sex variation in the prevalence of exercise-induced pulmonary haemorrhage in racing Quarter horses. Res Vet Sci 1986;40:406-407.

    9. Voynick BT, Sweeney CR. Exercised-induced pulmonary hemorrhage in polo and racing horses. JAVMA 1986;188:301-302.

    10. Singer ER, Barnes J, Saxby F, et al. Injuries in the event horse: training versus competition. Vet J 2008;175:76-81.

    11. Newton JR, Wood JL. Evidence of an association between inflammatory airway disease and EIPH in young Thoroughbreds during training. Equine Vet J Suppl 2002:417-424.

    12. Hinchcliff KW, Jackson MA, Morley PS, et al. Association between exercise-induced pulmonary hemorrhage and performance in Thoroughbred racehorses. JAVMA 2005;227:768-774.

    13. Cardwell J. Risk factors for EIPH in National hunt racehorses. Proc Dorothy Russell Havemeyer Foundation Workshop Exercise-Induced Pulmonary Hemorrhage 2008:6.

    14. Hinchcliff KW, Jackson MA, Brown JA, et al. Tracheobronchoscopic assessment of exercise-induced pulmonary hemorrhage in horses. Am J Vet Res 2005;66:596-598.

    15. Meyer TS, Fedde MR, Gaughan EM, et al. Quantification of exercise-induced pulmonary haemorrhage with bronchoalveolar lavage. Equine Vet J 1998;30:284-288.

    16. Birks EK, Durando MM. EIPH combination medications in North America: observations from a racetrack study. Proc Dorothy Russell Havemeyer Foundation Workshop Exercise-Induced Pulmonary Hemorrhage 2008:18.

    17. Whitwell KE, Greet TRC. Collection and evaluation of tracheobronchial washes in the horse. Equine Vet J 1984;16:499-508.

    18. O’Callaghan MW, Hornof WJ, Fisher PE, et al. Exercise-induced pulmonary haemorrhage in the horses: results of a detailed clinical, post mortem and imaging study. VII. Ventilation/perfusion scintigraphy in horses with EIPH. Equine Vet J 1987;19:423-427.

    19. O'Callaghan MW, Pascoe JR, Tyler WS, et al. Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. V. Microscopic observations. Equine Vet J 1987;19:411-418.

    20. O'Callaghan MW, Pascoe JR, Tyler WS, et al. Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. VIII. Conclusions and implications. Equine Vet J 1987;19:428-434.

    21. West JB, Mathieu-Costello O, Jones JH, et al. Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage. J Appl Physiol 1993;75:1097-1109.

    22. Williams KJ, Derksen FJ, de Feijter-Rupp H, et al. Regional pulmonary veno-occlusion: a newly identified lesion of equine exercise-induced pulmonary hemorrhage. Vet Pathol 2008;45:316-326.

    23. Johnson JE, Perkett EA, Meyrick B. Pulmonary veins and bronchial vessels undergo remodeling in sustained pulmonary hypertension induced by continuous air embolization into sheep. Exp Lung Res 1997;23:459-473.

    24. Manohar M, Hutchens E, Coney E. Furosemide attenuates the exercise-induced rise in pulmonary capillary blood pressure in horses. Equine Vet J 1994;26:51-54.

    25. Bernard SL, Glenny RW, Erickson HH, et al. Minimal redistribution of pulmonary blood flow with exercise in racehorses. J Appl Physiol 1996;81:1062-1070.

    26. Derksen FJ, Williams KJ, Uhal BD, et al. Pulmonary response to airway instillation of autologous blood in horses. Equine Vet J 2007;39:334-339.

    27. Birks EK. Vasodilator drugs and their impact on EIPH in horses. Proc World Equine Airway Symp 2005:65-68.

    28. Kindig CA, McDonough P, Fenton G, et al. Efficacy of nasal strip and furosemide in mitigating EIPH in Thoroughbred horses. J Appl Physiol 2001;91:1396-1400.

    29. Hinchcliff KW, Morley PS, Guthrie AJ. Efficacy of furosemide for prevention of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses. JAVMA 2009;235:76-82.

    30. Zawadzkas XA, Sides RH, Bayly WM. Is improved high speed performance following furosemide administration due to diuresis-induced weight loss or reduced severity of exercise-induced pulmonary haemorrhage? Equine Vet J Suppl 2006:291-293.

    31. Holcombe SJ, Berney C, Cornelisse CJ, et al. Effect of commercially available nasal strips on airway resistance in exercising horses. Am J Vet Res 2002;63:1101-1105.

    32. Pascoe JR, McCabe AE, Franti CE, et al. Efficacy of furosemide in the treatment of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses. Am J Vet Res 1985;46:2000-2003.

    33. Geor RJ, Ommundson L, Fenton G, et al. Effects of an external nasal strip and furosemide on pulmonary haemorrhage in Thoroughbreds following high-intensity exercise. Equine Vet J 2001;33:577-584.

    34. Valdez SC, Nieto JE, Spier SJ, et al. Effect of an external nasal dilator strip on cytologic characteristics of bronchoalveolar lavage fluid in Thoroughbred racehorses. JAVMA 2004;224:558-561.

    35. Erickson HH, Hildreth TS. Novel and emerging therapies for EIPH. Proc Am College Vet Intern Med Forum 2004:734-736.

    36. Sweeney CR, Soma LR. Exercise-induced pulmonary hemorrhage in Thoroughbred horses: response to furosemide or hesperidin-citrus bioflavinoids. JAVMA 1984;185:195-197.

    37. Padilla DJ, Epp TS, McDonough P, et al. Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in Thoroughbred horses. Equine Vet J Suppl 2006:198-203.

    38. Manohar M, Goetz TE, Rothenbaum P, et al. Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses. J Vet Pharmacol Ther 2000;23:389-395.

    39. Sweeney CR, Hall J, Fisher JR, et al. Efficacy of water vapor-saturated air in the treatment of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses. Am J Vet Res 1988;49:1705-1707.

    40. Manohar M, Goetz TE, Rothenbaum P, et al. Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of furosemide in strenuously exercising Thoroughbred horses. Equine Vet J 2001;33:354-359.

    41. Kindig CA, McDonough P, Finley MR, et al. NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses. J Appl Physiol 2001;91:2674-2678.

    References »

    NEXT: Flea Control: Real Cases: Fleas in a Flash!

    CETEST This course is approved for 3.0 CE credits

    Start Test

    didyouknow

    Did you know... Indirect methods of blood pressure measurement are the most practical but are subject to user error, so competency and following a standard protocol are very important.Read More

    These Care Guides are written to help your clients understand common conditions. They are formatted to print and give to your clients for their information.

    Stay on top of all our latest content — sign up for the Vetlearn newsletters.
    • More
    Subscribe