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Journal of applied physiology (Bethesda, Md. : 1985)1993; 75(3); 1097-1109; doi: 10.1152/jappl.1993.75.3.1097

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.
Publication Date: 1993-09-01 PubMed ID: 8226517DOI: 10.1152/jappl.1993.75.3.1097Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates why bleeding into lungs occurs in thoroughbred horses during exercise, concluding that this experience, known as exercise-induced pulmonary hemorrhage (EIPH), is caused by stress failure in the lungs’ capillaries.

Research Methodology

  • The research involved three thoroughbred horses known to have EIPH.
  • The horses were made to gallop on a treadmill and then euthanized intravenously with barbiturate.
  • Their lungs were then removed, inflated, and prepared for electron microscopy, a technique that provides increased resolution for detailed examination.

Research Findings

  • The researchers conducted an ultrastructural study providing extensive insights into the cell structure and organization.
  • The results showed evidence of stress failure in the capillaries of the horses’ lungs.
  • Findings included disruptions in capillary endothelial and alveolar epithelial layers, accumulations of red blood cells in the lung’s wall interstitium, the presence of protein-rich fluid and red blood cells in alveolar spaces, interstitial edema, and the protrusion of fluid-filled endothelia into the capillary lumen.
  • The team noted that the observed changes align with the transformations they previously discovered in rabbit lungs subject to high capillary pressures.

Further Observations & Calculations

  • The researchers had difficulty finding actual breaks in the endothelium and epithelium, which were often associated with platelets and white blood cells that seemed to be clogging these fracture points.
  • The small number of such breaks was attributed to their reversibility when pressure was reduced and to the delay (60-70 mins) between the horses’ gallop and the commencement of lung fixation.
  • The stress on the capillary walls was calculated from the measurements of pulmonary vascular pressures (in a companion study) and the measurements of blood-gas barrier thickness and capillary curvature radius.
  • The recorded value obtained via these calculations exceeded the breaking stress of most soft tissues.

Research Conclusion

  • The team concluded that the EIPH in thoroughbred horses during exercise is caused by stress failure in the pulmonary capillaries.

Cite This Article

APA
West JB, Mathieu-Costello O, Jones JH, Birks EK, Logemann RB, Pascoe JR, Tyler WS. (1993). Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage. J Appl Physiol (1985), 75(3), 1097-1109. https://doi.org/10.1152/jappl.1993.75.3.1097

Publication

ISSN: 8750-7587
NlmUniqueID: 8502536
Country: United States
Language: English
Volume: 75
Issue: 3
Pages: 1097-1109

Researcher Affiliations

West, J B
  • Department of Medicine, School of Medicine, University of California, San Diego, La Jolla 92093-0623.
Mathieu-Costello, O
    Jones, J H
      Birks, E K
        Logemann, R B
          Pascoe, J R
            Tyler, W S

              MeSH Terms

              • Animals
              • Blood-Air Barrier
              • Capillaries / pathology
              • Capillaries / physiopathology
              • Female
              • Hemorrhage / etiology
              • Hemorrhage / physiopathology
              • Hemorrhage / veterinary
              • Horse Diseases / etiology
              • Horse Diseases / pathology
              • Horse Diseases / physiopathology
              • Horses
              • Lung / ultrastructure
              • Lung Diseases / etiology
              • Lung Diseases / physiopathology
              • Lung Diseases / veterinary
              • Male
              • Microscopy, Electron
              • Pilot Projects
              • Pulmonary Circulation
              • Running
              • Stress, Mechanical

              Citations

              This article has been cited 45 times.
              1. Rocchigiani G, Verin R, Uzal FA, Singer ER, Pregel P, Ressel L, Ricci E. Pulmonary bleeding in racehorses: A gross, histologic, and ultrastructural comparison of exercise-induced pulmonary hemorrhage and exercise-associated fatal pulmonary hemorrhage. Vet Pathol 2022 Nov;59(6):973-982.
                doi: 10.1177/03009858221117859pubmed: 35972142google scholar: lookup
              2. Mazan M. Equine exercise physiology-challenges to the respiratory system. Anim Front 2022 Jun;12(3):15-24.
                doi: 10.1093/af/vfac035pubmed: 35711503google scholar: lookup
              3. Duke JW, Lewandowski AJ, Abman SH, Lovering AT. Physiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm. J Physiol 2022 Feb;600(3):463-482.
                doi: 10.1113/JP281848pubmed: 34961925google scholar: lookup
              4. Cruces P, Retamal J, Hurtado DE, Erranz B, Iturrieta P, González C, Díaz F. A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection. Crit Care 2020 Aug 10;24(1):494.
                doi: 10.1186/s13054-020-03197-7pubmed: 32778136google scholar: lookup
              5. Leiby KL, Raredon MSB, Niklason LE. Bioengineering the Blood-gas Barrier. Compr Physiol 2020 Mar 12;10(2):415-452.
                doi: 10.1002/cphy.c190026pubmed: 32163210google scholar: lookup
              6. Blott S, Cunningham H, Malkowski L, Brown A, Rauch C. A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse. Genes (Basel) 2019 Nov 1;10(11).
                doi: 10.3390/genes10110880pubmed: 31683933google scholar: lookup
              7. Nugent K, Dobbe L, Rahman R, Elmassry M, Paz P. Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review. J Thorac Dis 2019 Sep;11(9):4031-4038.
                doi: 10.21037/jtd.2019.09.02pubmed: 31656679google scholar: lookup
              8. Friedrich EE, Hong Z, Xiong S, Zhong M, Di A, Rehman J, Komarova YA, Malik AB. Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions. Proc Natl Acad Sci U S A 2019 Jun 25;116(26):12980-12985.
                doi: 10.1073/pnas.1902165116pubmed: 31186359google scholar: lookup
              9. Smith R, Ormerod JOM, Sabharwal N, Kipps C. Swimming-induced pulmonary edema: current perspectives. Open Access J Sports Med 2018;9:131-137.
                doi: 10.2147/OAJSM.S140028pubmed: 30100770google scholar: lookup
              10. Poole DC, Erickson HH. Exercise-induced pulmonary hemorrhage: where are we now?. Vet Med (Auckl) 2016;7:133-148.
                doi: 10.2147/VMRR.S120421pubmed: 30050846google scholar: lookup
              11. Mellor DJ, Beausoleil NJ. Equine Welfare during Exercise: An Evaluation of Breathing, Breathlessness and Bridles. Animals (Basel) 2017 May 26;7(6).
                doi: 10.3390/ani7060041pubmed: 28587125google scholar: lookup
              12. Kruavit A, Jain M, Fielding D, Heraganahally S. Exercise-induced endobronchial hemorrhage: a rare clinical presentation. Respirol Case Rep 2016 Jul;4(4):e00163.
                doi: 10.1002/rcr2.163pubmed: 27512564google scholar: lookup
              13. Bove AA. Pulmonary Aspects of Exercise and Sports. Methodist Debakey Cardiovasc J 2016 Apr-Jun;12(2):93-7.
                doi: 10.14797/mdcj-12-2-93pubmed: 27486491google scholar: lookup
              14. Léguillette R, Steinmann M, Bond SL, Stanton B. Tracheobronchoscopic Assessment of Exercise-Induced Pulmonary Hemorrhage and Airway Inflammation in Barrel Racing Horses. J Vet Intern Med 2016 Jul;30(4):1327-32.
                doi: 10.1111/jvim.13959pubmed: 27278854google scholar: lookup
              15. Kim DS, Lee M, Kwon OJ, Jeong I, Son JW, Na MJ, Kwon SJ. A 45-Year-Old Man With Recurrent Dyspnea and Hemoptysis during Exercise: Exercise-Induced Pulmonary Hemorrhage/Edema. Tuberc Respir Dis (Seoul) 2015 Oct;78(4):375-9.
                doi: 10.4046/trd.2015.78.4.375pubmed: 26508928google scholar: lookup
              16. Yamanashi H, Koyamatsu J, Nobuyoshi M, Murase K, Maeda T. Exercise-Induced Pulmonary Edema in a Triathlon. Case Rep Med 2015;2015:968152.
                doi: 10.1155/2015/968152pubmed: 26229538google scholar: lookup
              17. Hinchcliff KW, Couetil LL, Knight PK, Morley PS, Robinson NE, Sweeney CR, van Erck E. Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine consensus statement. J Vet Intern Med 2015 May-Jun;29(3):743-58.
                doi: 10.1111/jvim.12593pubmed: 25996660google scholar: lookup
              18. Adir Y, Bove AA. Lung injury related to extreme environments. Eur Respir Rev 2014 Dec;23(134):416-26.
                doi: 10.1183/09059180.00006214pubmed: 25445940google scholar: lookup
              19. Maina JN, Jimoh SA. Study of Stress Induced Failure of the Blood-gas Barrier and the Epithelial-epithelial Cells Connections of the Lung of the Domestic Fowl, Gallus gallus Variant Domesticus after Vascular Perfusion. Biomed Eng Comput Biol 2013;5:77-88.
                doi: 10.4137/BECB.S12988pubmed: 25288905google scholar: lookup
              20. Diwakar A, Schmidt GA. Exercise-induced pulmonary hemorrhage in a nonathlete: case report and review of physiology. Lung 2014 Apr;192(2):329-31.
                doi: 10.1007/s00408-014-9562-0pubmed: 24532148google scholar: lookup
              21. Vengust M, Staempfli H, Viel L, Swenson ER, Heigenhauser G. Acetazolamide attenuates transvascular fluid flux in equine lungs during intense exercise. J Physiol 2013 Sep 15;591(18):4499-513.
                doi: 10.1113/jphysiol.2013.257956pubmed: 23818694google scholar: lookup
              22. Paralikar SJ. High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment. Indian J Occup Environ Med 2012 May;16(2):59-62.
                doi: 10.4103/0019-5278.107066pubmed: 23580834google scholar: lookup
              23. Naeije R, Chesler N. Pulmonary circulation at exercise. Compr Physiol 2012 Jan;2(1):711-41.
                doi: 10.1002/cphy.c100091pubmed: 23105961google scholar: lookup
              24. Perez-Moreno CI, Couëtil LL, Pratt SM, Ochoa-Acuña HG, Raskin RE, Russell MA. Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in Standardbred racehorses. Can Vet J 2009 Aug;50(8):821-7.
                pubmed: 19881919
              25. West JB. Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution. Am J Physiol Regul Integr Comp Physiol 2009 Dec;297(6):R1625-34.
                doi: 10.1152/ajpregu.00459.2009pubmed: 19793953google scholar: lookup
              26. Lovering AT, Haverkamp HC, Romer LM, Hokanson JS, Eldridge MW. Transpulmonary passage of 99mTc macroaggregated albumin in healthy humans at rest and during maximal exercise. J Appl Physiol (1985) 2009 Jun;106(6):1986-92.
              27. MacNutt MJ, Guenette JA, Witt JD, Yuan R, Mayo JR, McKenzie DC. Intense hypoxic cycle exercise does not alter lung density in competitive male cyclists. Eur J Appl Physiol 2007 Apr;99(6):623-31.
                doi: 10.1007/s00421-006-0388-1pubmed: 17219166google scholar: lookup
              28. Ghio AJ, Ghio C, Bassett M. Exercise-induced pulmonary hemorrhage after running a marathon. Lung 2006 Nov-Dec;184(6):331-3.
                doi: 10.1007/s00408-006-0023-2pubmed: 17086462google scholar: lookup
              29. West JB. Vulnerability of pulmonary capillaries during severe exercise. Br J Sports Med 2006 Oct;40(10):821.
                doi: 10.1136/bjsm.2006.028886pubmed: 17021008google scholar: lookup
              30. Hodges AN, Mayo JR, McKenzie DC. Pulmonary oedema following exercise in humans. Sports Med 2006;36(6):501-12.
              31. Tennent-Brown BS, Goetz TE, Manohar M, Hassan AS, Freeman DE, Bundy JS, Evans MR. Hyperhydration prior to a simulated second day of the 3-day moderate intensity equestrian competition does not cause arterial hypoxemia in Thoroughbred horses. Eur J Appl Physiol 2006 Jul;97(4):462-70.
                doi: 10.1007/s00421-006-0191-zpubmed: 16685549google scholar: lookup
              32. Vengust M, Staempfli H, Viel L, Heigenhauser G. Transvascular fluid flux from the pulmonary vasculature at rest and during exercise in horses. J Physiol 2006 Jan 15;570(Pt 2):397-405.
                doi: 10.1113/jphysiol.2005.098723pubmed: 16269434google scholar: lookup
              33. Manohar M, Goetz TE, Hassan AS. Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses. Eur J Appl Physiol 2005 Jan;93(4):480-8.
                doi: 10.1007/s00421-004-1213-3pubmed: 15455236google scholar: lookup
              34. Marini JJ, Hotchkiss JR, Broccard AF. Bench-to-bedside review: microvascular and airspace linkage in ventilator-induced lung injury. Crit Care 2003 Dec;7(6):435-44.
                doi: 10.1186/cc2392pubmed: 14624683google scholar: lookup
              35. Hackett RP, Ducharme NG, Gleed RD, Mitchell L, Soderholm LV, Erickson BK, Erb HN. Do Thoroughbred and Standardbred horses have similar increases in pulmonary vascular pressures during exertion?. Can J Vet Res 2003 Oct;67(4):291-6.
                pubmed: 14620866
              36. Prefaut C, Durand F, Mucci P, Caillaud C. Exercise-induced arterial hypoxaemia in athletes: a review. Sports Med 2000 Jul;30(1):47-61.
              37. Harms CA, McClaran SR, Nickele GA, Pegelow DF, Nelson WB, Dempsey JA. Exercise-induced arterial hypoxaemia in healthy young women. J Physiol 1998 Mar 1;507 ( Pt 2)(Pt 2):619-28.
              38. Mills PC, Marlin DJ, Demoncheaux E, Scott C, Casas I, Smith NC, Higenbottam T. Nitric oxide and exercise in the horse. J Physiol 1996 Sep 15;495 ( Pt 3)(Pt 3):863-74.
                doi: 10.1113/jphysiol.1996.sp021638pubmed: 8887788google scholar: lookup
              39. West JB, Mathieu-Costello O. Stress failure of pulmonary capillaries as a limiting factor for maximal exercise. Eur J Appl Physiol Occup Physiol 1995;70(2):99-108.
                doi: 10.1007/BF00361536pubmed: 7768245google scholar: lookup
              40. Reddy AC, Kaloss AM, Jeong HW, Carvallo-Chaigneau FR. Pathogenesis, histopathology, and mechanisms of pulmonary pathology secondary to chronic left heart failure in animals. J Vet Diagn Invest 2026 Jan 29;:10406387251415577.
                doi: 10.1177/10406387251415577pubmed: 41612792google scholar: lookup
              41. Boesch JM, Gleed RD, Buss PE, Tordiffe ASW, Zeiler GE, Miller MA, Viljoen F, Harvey BH, Parry SA, Meyer LCR. Etorphine induces pathophysiology in immobilized white rhinoceros through sympathomimesis that is attenuated by butorphanol. Conserv Physiol 2025;13(1):coaf009.
                doi: 10.1093/conphys/coaf009pubmed: 40196708google scholar: lookup
              42. Bayly WM, Leguillette R, Sides RH, Massie S, Guigand C, Jones KB, Warlick LM, Thueson EL, Troudt TA, Slocombe RF, Jones JH. Equine exercise-induced pulmonary hemorrhage: the role of high left-heart pressures secondary to exercise-induced hypervolemia, and high inspiratory pressures. J Appl Physiol (1985) 2024 Nov 1;137(5):1359-1373.
              43. Dumont R, Touzet C, Gomes E, Le Boedec K. Treatment of recurrent hunting-associated respiratory distress episodes in 2 dogs. J Vet Intern Med 2023 Nov-Dec;37(6):2514-2519.
                doi: 10.1111/jvim.16665pubmed: 37878243google scholar: lookup
              44. Hopkins SR, Stickland MK. The Pulmonary Vasculature. Semin Respir Crit Care Med 2023 Oct;44(5):538-554.
                doi: 10.1055/s-0043-1770059pubmed: 37816344google scholar: lookup
              45. Nath LC, Elliott A, La Gerche A, Weir J, Forbes G, Thomas G, Franklin S. Associations between postrace atrial fibrillation and measures of performance, racing history and airway disease in horses. J Vet Intern Med 2023 Nov-Dec;37(6):2573-2583.
                doi: 10.1111/jvim.16878pubmed: 37740606google scholar: lookup