The effects of furosemide on pulmonary transmural pressure and exercise-induced pulmonary hemorrhage in supramaximally exercising thoroughbred racehorses.

Overview

• This study investigated how furosemide, a diuretic medication, impacts pulmonary transmural pressure and exercise-induced pulmonary hemorrhage (EIPH) in Thoroughbred racehorses undergoing supramaximal exercise.
• The research demonstrated that furosemide reduces the pulmonary pressures associated with stress failure and decreases the severity of hemorrhage, although it does not completely prevent these effects.

Background and Purpose

• During maximal or supramaximal exercise, the pulmonary capillaries of horses experience extremely high pressures, which may lead to capillary stress failure causing EIPH—bleeding in the lungs.
• Pulmonary transmural pressure (Ptm) is the pressure difference across the capillary walls and is a key factor in causing vascular damage.
• Furosemide, a diuretic commonly used in racehorses, is known to reduce pulmonary arterial pressure (PAP) and pulmonary wedge pressure (PAW), potentially lowering Ptm and thus EIPH severity.
• The objective was to precisely assess the effect of furosemide on pulmonary pressures, especially Ptm, and the resulting EIPH during intense treadmill exercise beyond the horses’ maximal oxygen consumption (120% V̇O2max).

Methods

• Subjects:
  • Six retired but fit Thoroughbred horses with consistent high-grade EIPH (Grade ≥ 2).
• Design:
  • Controlled crossover experiment where each horse completed treadmill tests both before and 4 hours after receiving IV furosemide (0.5 mg/kg).
  • Exercise was standardized at 120% of maximal oxygen uptake (supramaximal intensity).
• Measurements:
  • Catheters measured pulmonary arterial pressure (PAP) and pulmonary wedge pressure (PAW).
  • An esophageal catheter measured intrapleural pressure (Ppl), the pressure inside the chest cavity.
  • Pulmonary capillary pressure (Pcap) was estimated as the average of PAP and PAW.
  • Ptm was calculated as the difference between Pcap and Ppl.
  • The duration when Ptm exceeded a failure threshold of 75 mm Hg was tracked to quantify stress failure risk.
  • Blood volume (BV) and plasma volume (PV) were measured to assess fluid changes.
  • EIPH severity was evaluated using tracheoendoscopic scoring and bronchoalveolar lavage red blood cell count differences (ΔBALRBC) before and after exercise.
• Data analysis was done by paired t-tests to compare control and furosemide treatments, with significance at P < 0.05.

Key Findings

• Furosemide significantly reduced:
  • Mean PAP (pulmonary arterial pressure)
  • PAW (pulmonary wedge pressure)
  • Estimated pulmonary capillary pressure (Pcap)
• Intrapleural pressure (Ppl) was unaffected by furosemide.
• Because Ppl stayed the same, the reduction in Pcap led to a significant decrease in both maximum and minimum pulmonary transmural pressure (Ptm).
• The time that Ptm exceeded the critical threshold of 75 mm Hg dropped by about 45%, from 57% to 31% of exercise duration, indicating less stress on pulmonary capillaries.
• Furosemide did not change total blood volume (BV) or plasma volume (PV) when measured 4 hours post-treatment.
• EIPH severity as measured by endoscopic score and ΔBALRBC was significantly reduced after furosemide treatment.
• Despite reductions, Ptm still exceeded the threshold for stress failure some of the time, and mild EIPH persisted even with furosemide.

Conclusions and Implications

• Furosemide effectively lowers pulmonary vascular pressures and reduces the mechanical stress on pulmonary capillaries during intense exercise.
• This reduction translates into a meaningful decrease in the severity of exercise-induced pulmonary hemorrhage in affected Thoroughbred racehorses.
• However, furosemide does not completely prevent elevated transmural pressures nor fully eliminate EIPH, suggesting other factors contribute to the condition or that pressures remain high enough to cause some vascular damage even after treatment.
• Management of EIPH with furosemide may be beneficial but is not fully protective, highlighting the need for additional strategies or interventions for pulmonary health in equine athletes during maximal effort exercise.