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Journal of applied physiology (Bethesda, Md. : 1985)2024; 137(5); 1359-1373; doi: 10.1152/japplphysiol.00575.2023

Equine exercise-induced pulmonary hemorrhage: the role of high left-heart pressures secondary to exercise-induced hypervolemia, and high inspiratory pressures.

Abstract: Exercise-induced pulmonary hemorrhage (EIPH) is common in racehorses. Stress failure of the blood-gas barrier causes EIPH when the transmural pulmonary capillary (Pcap)-alveolar pressure difference (Ptm) exceeds the barrier's stress failure threshold. Why Pcap increases is incompletely understood. We hypothesized that alterations in blood volume (BV) could affect left ventricular (LV) and pulmonary arterial wedge (PAW) pressures and Pcap, and correspondingly affect EIPH severity. Six thoroughbreds with EIPH exercised at the same treadmill speed (≈11.9 m/s [11.1, 12.2]; median [IQR]) before (≈119% V̇o; B), 2 h after 14 L depletion of blood (≈132% V̇o; D), and 2 h after reinfusing the blood (≈111% V̇o; R). LV, pulmonary arterial (PAP), PAW, and intrapleural (Ppl) pressures were measured throughout exercise. Pcap = (PAP + PAW)/2 and Ptm = (Pcap - Ppl). EIPH severity was assessed 60 min postexercise by tracheoendoscopy (EIPHgrade) and bronchoalveolar lavage erythrocyte number (BALRBC). A mixed-effect model and Tukey post hoc test analyzed the effects of BV changes on LV, PAW, Pcap, Ppl, Ptm, and EIPH. ≤ 0.05 was significant. Peak intrapleural inspiratory pressure (Ppl) was high (-41 mmHg), unaffected by changes in BV ( = 0.44), and did not contribute to fluctuations in Ptm and EIPH severity, whereas changes in BV did (EIPHgrade: = 0.01, BALRBC: = 0.003). EIPH prevalence was 100% with B and R but 50% with D. MaxPtm was not different between B (146 mmHg [140, 151]) and R (151 mmHg [137, 160]) but was lower for D (128 mmHg [127, 130]; B: = 0.005, R: = 0.02). Vascular pressures and Ppl fluctuated constantly during exercise and independently influenced Ptm. Left ventricular end diastolic (LVED) pressure was correlated with Ptm ( = 0.90, = 0.03) and EIPH = 0.82, = 0.004). Exercise BV was strongly correlated with EIPH severity in racehorses ( = 0.86, = 0.009). Hypervolemia induced by the infusion of erythrocyte-rich blood stored in the spleen is normal in high-speed thoroughbred exercise and increases capillary-alveolar transmural pressure (Ptm), leading to exercise-induced pulmonary hemorrhage (EIPH). In this study, decreasing blood volume reduced Ptm and EIPH. Large negative inspiratory pressures also contribute to high Ptm and the occurrence of EIPH. Ptm is dynamic and oscillates constantly during exercise. A significant relationship existed between circulating blood volume and EIPH severity in racehorses.
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Publication Date: 2024-10-10 PubMed ID: 39388286PubMed Central: PMC11573257DOI: 10.1152/japplphysiol.00575.2023Google 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.

Overview

  • This research investigates how changes in blood volume and inspiratory pressures during high-speed exercise affect pulmonary capillary pressures and the severity of exercise-induced pulmonary hemorrhage (EIPH) in racehorses.
  • The study found that increased blood volume (hypervolemia) raises left heart and pulmonary pressures, thereby increasing the pressure across the pulmonary capillary-alveolar barrier, which contributes to EIPH severity.

Background and Rationale

  • EIPH is a common condition in racehorses where blood leaks into the lungs during intense exercise.
  • EIPH is caused by “stress failure” of the blood-gas barrier in lung capillaries when the difference between pulmonary capillary pressure and alveolar pressure (transmural pressure, Ptm) exceeds a threshold.
  • Why pulmonary capillary pressure (Pcap) increases during exercise remains incompletely understood.
  • The researchers hypothesized that alterations in blood volume (BV) during intense exercise may change left ventricular (LV) and pulmonary arterial wedge (PAW) pressures affecting Pcap and thus EIPH severity.

Study Design and Methods

  • Subjects: Six thoroughbred racehorses with known EIPH.
  • Experimental Conditions: Each horse exercised on a treadmill at approximately 11.9 m/s under three conditions:
    • Before blood volume manipulation (baseline, B; BV ~119% of resting oxygen consumption VO2).
    • After removal of 14 liters of blood (depletion, D; BV ~132% VO2).
    • After reinfusion of the removed blood (reinfusion, R; BV ~111% VO2).
  • Measured variables during exercise:
    • Left ventricular (LV) pressure.
    • Pulmonary arterial pressure (PAP).
    • Pulmonary arterial wedge pressure (PAW).
    • Intrapleural pressure (Ppl), especially inspiratory pressure.
  • Calculated variables:
    • Pcap = (PAP + PAW)/2, pulmonary capillary pressure.
    • Ptm = Pcap – Ppl, transmural pressure across pulmonary capillary-alveolar barrier.
  • EIPH severity was assessed 60 minutes postexercise using:
    • Tracheoendoscopy score (EIPHgrade).
    • Bronchoalveolar lavage erythrocyte number (BALRBC) as a quantitative marker.
  • Statistical analysis included mixed-effect modeling and post hoc Tukey tests for the effect of BV changes on measured pressures and EIPH severity.
  • Statistical significance was set at p ≤ 0.05.

Key Findings

  • Intrapleural inspiratory pressure (Ppl):
    • Peak inspiratory negative pressure averaged -41 mmHg, indicating very high inspiratory effort.
    • Ppl did NOT significantly change with alterations in blood volume (p = 0.44).
    • Thus, Ppl did not explain changes in transmural pressure (Ptm) or EIPH severity across BV conditions.
  • Blood volume effects on pressures:
    • EIPH severity (both endoscopic scores and BAL RBC counts) significantly changed with blood volume alterations (EIPHgrade p = 0.01, BALRBC p = 0.003).
    • All horses exhibited EIPH before (B) and after reinfusion (R), but only 50% showed EIPH after blood depletion (D).
    • Maximum transmural pressure (MaxPtm):
      • B (baseline): median 146 mmHg (140, 151).
      • R (reinfusion): median 151 mmHg (137, 160).
      • D (depleted blood volume): significantly lower at 128 mmHg (127,130) compared to B (p = 0.005) and R (p = 0.02).
    • Vascular pressures and intrapleural pressure fluctuated continuously during exercise and independently influenced Ptm.
    • Left ventricular end diastolic pressure (LVED) strongly correlated with Ptm (r = 0.90, p=0.03) and EIPH severity (r = 0.82, p=0.004), linking left heart pressure to pulmonary capillary stress and hemorrhage.
  • Blood volume and EIPH severity correlation:
    • Exercise blood volume was strongly correlated with EIPH severity (r = 0.86, p = 0.009).
    • Hypervolemia, driven by spleen-released erythrocyte-rich blood during high-speed exercise, increases capillary-alveolar transmural pressure leading to EIPH.

Conclusions and Implications

  • Exercise-induced hypervolemia (increased blood volume) is a normal physiological response in thoroughbred racehorses during high-speed exercise, caused by spleen contraction releasing stored erythrocyte-rich blood.
  • This hypervolemia raises left heart pressures and pulmonary capillary pressures, increasing Ptm beyond the threshold for stress failure, thus promoting EIPH.
  • Reducing blood volume through depletion reduces Ptm and the severity and prevalence of EIPH, indicating a direct mechanistic link between blood volume and hemorrhage.
  • Very negative inspiratory pressures contribute to high Ptm but do not change with blood volume, suggesting that they are an independent factor in EIPH development.
  • Ptm is dynamic and oscillates continuously during exercise due to fluctuations in both vascular and pleural pressures.
  • Therapeutic or management strategies could consider modulating blood volume or left heart pressures to mitigate EIPH severity in racehorses.

Summary

  • This study elucidates the physiological mechanisms behind EIPH in racehorses, emphasizing the role of exercise-induced increases in blood volume and left-heart pressures in raising pulmonary capillary-alveolar transmural pressure beyond safe limits.
  • It highlights that while intense inspiratory efforts also elevate transmural pressure, the modulation of blood volume is key in controlling EIPH severity.

Cite This Article

APA
Bayly WM, Leguillette R, Sides RH, Massie S, Guigand C, Jones KB, Warlick LM, Thueson EL, Troudt TA, Slocombe RF, Jones JH. (2024). 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), 137(5), 1359-1373. https://doi.org/10.1152/japplphysiol.00575.2023

Publication

Journal of applied physiology (Bethesda, Md. : 1985)
ISSN: 1522-1601
NlmUniqueID: 8502536
Country: United States
Language: English
Volume: 137
Issue: 5
Pages: 1359-1373

Researcher Affiliations

Bayly, Warwick M
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Leguillette, Renaud
  • Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Sides, Raymond H
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Massie, Shannon
  • Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Guigand, Charline
  • Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Jones, K Blythe
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Warlick, Linnea M
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Thueson, Emily L
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Troudt, Tristan A
  • Department of Veterinary Clinical Sciences, Washington State University, College of Veterinary Medicine, Pullman, Washington, United States.
Slocombe, Ronald F
  • School of Veterinary and Agricultural Science, University of Melbourne, Werribee, Victoria, Australia.
Jones, James H
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.

MeSH Terms

  • Animals
  • Horses
  • Physical Conditioning, Animal / physiology
  • Hemorrhage / physiopathology
  • Blood Volume / physiology
  • Male
  • Lung Diseases / physiopathology
  • Lung Diseases / etiology
  • Lung / physiopathology
  • Female
  • Pulmonary Wedge Pressure / physiology
  • Horse Diseases / physiopathology
  • Inhalation / physiology
  • Blood Pressure / physiology
  • Ventricular Function, Left / physiology

Grant Funding

  • The Grayson-Jockey Club Research Foundation
  • The Washington State Equine Research Fund
  • The Calgary Chair in Sports Medicine

Conflict of Interest Statement

No conflicts of interest, financial or otherwise, are declared by the authors.

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Citations

This article has been cited 1 times.
  1. Park T, Hong S, Murray L, Lee J, Shah A, Mesa JC, Lee H, Couetil L, Lee CH. Wearable smart textile band for continuous equine health monitoring. Biosens Bioelectron 2026 Jan 15;292:118073.
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