Topic:Exercise-Induced Pulmonary Hemorrhage
Exercise-Induced Pulmonary Hemorrhage (EIPH) is a condition observed in horses, characterized by bleeding from the blood vessels within the lungs during or shortly after intense physical activity. This phenomenon is commonly identified in racing and performance horses. The condition is associated with the rupture of pulmonary capillaries, leading to the presence of blood in the airways. EIPH can affect a horse's respiratory efficiency and overall performance. Diagnosis is typically confirmed through endoscopic examination or detection of blood in the trachea post-exercise. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, management, and implications of EIPH in equine athletes.
Effects of exercise on markers of venous remodeling in lungs of horses. To determine the effects of 2 weeks of intense exercise on expression of markers of pulmonary venous remodeling in the caudodorsal and cranioventral regions of the lungs of horses. Methods: 6 horses. Methods: Tissue samples of the caudodorsal and cranioventral regions of lungs were obtained before and after conditioning and 2 weeks of intense exercise. Pulmonary veins were isolated, and a quantitative real-time PCR assay was used to determine mRNA expression of matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinase-1 and -2, collagen type I, tenascin-C, endothelin-1, platelet...
Quantification of several acidic drugs in equine serum using LC-MS-MS. The use of nonsteroidal antiinflammatory drugs in racehorses is allowed under most jurisdictions. Furosemide is administered to treat exercise-induced pulmonary hemorrhage. To help distinguish between therapeutic and illegal uses, racing regulatory bodies have set thresholds in serum for several drugs. The method for the simultaneous detection and quantification of furosemide, flunixin, ketoprofen, phenylbutazone and oxyphenbutazone using 500 µL of serum, and liquid extraction using diethyl ether : hexanes : dichloromethane followed by liquid chromatography tandem mass spectrometry quantitati...
Distribution of venous remodeling in exercise-induced pulmonary hemorrhage of horses follows reported blood flow distribution in the equine lung. Exercise-induced pulmonary hemorrhage (EIPH), which has been reported in humans and a variety of domestic animals following strenuous exercise, is most often documented in racehorses. Remodeling of pulmonary veins (VR) in equine EIPH was recently described, suggesting that it contributes to the pathogenesis of the disease. The cause of VR is unknown. We tested the hypothesis that the development of VR follows pulmonary blood flow distribution, preferentially occurring in the caudodorsal lung region. Furthermore, we hypothesized that VR underpins development of the other lesions of EIPH patholo...
Cohort study examining long-term respiratory health, career duration and racing performance in racehorses that undergo left-sided prosthetic laryngoplasty and ventriculocordectomy surgery for treatment of left-sided laryngeal hemiplegia. The risk of respiratory conditions, such as inflammatory airway disease (IAD) and exercise-induced pulmonary haemorrhage (EIPH), are thought to be higher in racehorses that undergo prosthetic laryngoplasty with ventriculocordectomy (PLVC) surgery to treat left-sided laryngeal hemiplegia (LLH) than in racehorses with normal laryngeal function. However, this has not been investigated formally owing to the difficulty of obtaining reliable follow-up data. Objective: To determine the incidence of respiratory conditions (IAD and EIPH), duration of racing career, number of starts and number of starts...
Association between circulating angiotensin-converting enzyme and exercise-induced pulmonary haemorrhage in Thoroughbred racehorses. Exercise-induced pulmonary haemorrhage has an impact on racehorse performance. Although endoscopic diagnosis (with or without the aid of bronchoalveolar lavage) is considered to be the standard diagnostic method for this condition, the use of biomarkers that could aid in quantifying risk and severity of the condition would represent an advance in equine sport medicine. This preliminary research investigated the use of angiotensin-converting enzyme (ACE) activity in plasma of racehorses and demonstrated that ACE activity is increased in horses with higher degrees of haemorrhage and is a promisi...
Pulmonary inflammation due to exercise-induced pulmonary haemorrhage in Thoroughbred colts during race training. This study investigated the putative roles of inflammation and platelet-activating factor (PAF) in exercise-induced pulmonary haemorrhage (EIPH). Two-year-old Thoroughbred colts (n=37) were exercised on a racetrack for 5months before commencement of the study. Each colt was then exercised at 15-16m/s over 800-1000m and broncho-alveolar lavage fluid (BALF) was collected 24h later. The colts were subsequently divided into two groups on the basis of BALF analysis; an EIPH-positive group (presence of haemosiderophages, n=23) and an EIPH-negative group (absence of haemosiderophages, n=14). BALF fro...
Exercise-induced pulmonary hemorrhage in horses: the role of pulmonary veins. While airway endoscopy and bronchoalveolar lavage are the methodsof 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 ple...
Risk factors for exercise-induced pulmonary haemorrhage in Thoroughbred racehorses. Risk factors for occult exercise-induced pulmonary haemorrhage (EIPH) are poorly defined or quantified. Objective: To investigate the importance of putative risk factors for EIPH amongst Thoroughbred racehorses in Australia. Methods: Tracheobronchoscopy was used to determine EIPH status of 744 Thoroughbred racehorses after flat racing in Melbourne, Australia. Horses were identified for study before racing, and over 50% of horses racing during the study period were examined. Statistical analysis included use of bivariate and multivariate logistic regression analysis to account for simultaneous ...
The effect of sildenafil citrate administration on selected physiological parameters of exercising Thoroughbred horses. Sildenafil, a phosphodiesterase-5 inhibitor vasodilator, increases cGMP concentrations by inhibiting enzymatic degradation. Marketed to treat erectile dysfunction in men, it also reduces pulmonary arterial pressure (PAP). Because it reduces PAP, sildenafil may enhance performance and/or prevent exercise induced-pulmonary haemorrhage (EIPH). Objective: To determine if sildenafil citrate administration altered commonly measured indices of performance or reduced EIPH in exercised horses. Methods: Thirteen athletically conditioned Thoroughbred horses (2 mares and 11 geldings, age 3-12 years) were ...
Effects of intravenous aminocaproic acid on exercise-induced pulmonary haemorrhage (EIPH). The antifibrinolytic, 6-aminohexanoic acid, also named aminocaproic acid (ACA), has been used empirically as a treatment for exercise-induced pulmonary haemorrhage (EIPH) on the unsubstantiated basis that transient coagulation dysfunction may contribute to its development. Objective: To assess the effect of ACA on bronchoalveolar lavage fluid (BALF) erythrocyte counts in horses performing treadmill exercise at an intensity greater than that needed to reach maximal oxygen consumption. Methods: Eight Thoroughbreds were exercised to fatigue 3 times on a 10% inclined treadmill at a speed for which...
Experimental mild pulmonary inflammation promotes the development of exercise-induced pulmonary haemorrhage. Histological studies of exercise-induced pulmonary haemorrhage (EIPH) reveals inflammatory infiltrates within areas of lung that contain haemorrhage. This has resulted in the hypothesis that pulmonary inflammation could cause EIPH or contribute to an increased risk or severity of EIPH. Objective: To determine whether experimentally-induced pulmonary inflammation predisposes the lung to haemorrhage during exercise, by evaluating the bronchoalveolar lavage (BAL) cytology of normal and inflamed regions of lung following high speed treadmill exercise. Methods: Transendoscopic airway inoculations o...
Repeated blood instillation into the airway of the horse does not cause pulmonary fibrosis. Exercise-induced pulmonary haemorrhage (EIPH) occurs in nearly all strenuously exercising horses. Recent studies have attempted to identify the role of free blood within the airspaces, in the lung fibrosis that develops within the lungs of EIPH horses. Objective: Repeated exposure of the equine lung to autologous blood results in lung fibrosis similar to that observed in spontaneous EIPH. Methods: Forty ml of autologous blood from the jugular vein was instilled into preselected lung regions of 6 horses one, 2, 3, 4 or 5 times at 2 week intervals, with 40 ml of saline instilled into the contral...
Thromboelastometric profiles of horses affected by exercise-induced pulmonary hemorrhages. Exercise-induced pulmonary hemorrhage (EIPH) commonly occurs in race horses. Thromboelastometry (TEM) investigates the whole hemostatic process by evaluating the viscoelastic properties of the blood clot from its formation to fibrinolysis. The aim of this study was to assess whether horses with EIPH have abnormal thromboelastometric profiles. Intrinsic and extrinsic pathways, fibrinogen activity and fibrinolysis were investigated by TEM before and after the race in negative controls and in horses on which EIPH was confirmed by bronchoscopy. Compared with controls, horses with EIPH had an incre...
Effect of frusemide on transvascular fluid fluxes across the lung in exercising horses. Frusemide (Fru) is widely prescribed for management of racehorses experiencing EIPH. The effect of Fru in the lung appears to be a reduction in transcapillary pressures and inhibition of the erythrocyte anion exchange, which may lead to attenuation of transpulmonary fluid fluxes during exercise. Objective: Treatment with Fru will attenuate transpulmonary fluid fluxes in horses during high intensity exercise. Methods: In a crossover study, 6 race-fit Standardbred horses were treated with 250 mg of Fru i.v. (FruTr) or placebo (Con) 4 h before exercise on a high speed treadmill until fatigue. Art...
Cytokine mRNA expressions after racing at a high altitude and at sea level in horses with exercise-induced pulmonary hemorrhage. To determine concentrations of cytokine mRNA in horses with exercise-induced pulmonary hemorrhage (EIPH) after racing. Methods: 97 Thoroughbreds. Methods: Following tracheobronchoscopy, the severity of EIPH was graded (scale of 0 to 4), and venous blood samples were collected from 10 horses in each grade. After RNA isolation and cDNA synthesis, real-time PCR assay was conducted to detect cytokinespecific mRNA for interleukin (IL)-1, IL-6, and IL-10; interferon (INF)-gamma; and tumor necrosis factor (TNF)-alpha. Results: Neither location nor grade of EIPH affected the expression of IL-1 and INF...
Effect of furosemide and furosemide-carbazochrome combination on exercise-induced pulmonary hemorrhage in Standardbred racehorses. The objective was to quantify the effect of furosemide and carbazochrome on exercise-induced pulmonary hemorrhage (EIPH) in Standardbred horses using red blood cell count and hemoglobin concentration in bronchoalveolar lavage (BAL) fluid. Six healthy Standardbred horses with prior evidence of EIPH performed a standardized treadmill test 4 h after administration of placebo, furosemide, or furosemide-carbazochrome combination. Red blood cell (RBC) counts and hemoglobin concentrations were determined on the BAL fluid. The RBC count in BAL ranges were (2903-26,025 cells/microL), (45-24,060 cells/m...
Regional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhage. Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Objective: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumula...
Efficacy of furosemide for prevention of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses. To evaluate the efficacy of furosemide for prevention of exercise-induced pulmonary hemorrhage (EIPH) in Thoroughbred racehorses under typical racing conditions. Methods: Randomized, placebo-controlled, blinded, crossover field trial. Methods: 167 Thoroughbred racehorses. Methods: Horses were allocated to race fields of 9 to 16 horses each and raced twice, 1 week apart, with each of the 2 races consisting of the same race field and distance. Each horse received furosemide (500 mg, IV) before one race and a placebo (saline solution) before the other, with the order of treatments randomly determ...
Regional pulmonary veno-occlusion: a newly identified lesion of equine exercise-induced pulmonary hemorrhage. Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylin-eosin, Masson...
Transverse and dorso-ventral changes in thoracic dimension during equine locomotion. Changes in shape of the equine thorax during locomotion are not well defined, although it has been shown recently that the transverse hemi-diameter changes its dimension by up to 80mm on the side of the trailing forelimb during gallop, despite minimal change in thoracic circumference. The aim of this project was to analyse transverse and dorso-ventral changes in shape of the thorax simultaneously, and to determine if leading limb, treadmill slope and speed have an effect on these shape changes. Reflective markers were placed on the horse's hemi-thorax and movement of the markers was recorded u...
Acute training in racing horses at two different levels of effort: A haemorheological analysis. During acute exercise several significant cardiovascular alterations take place, along with possible physiopathological consequences, such as Exercise Inducted Pulmonary Haemorrhage (EIPH). Given the relevance of blood rheology in the determination of flow resistance and its supposed participation in the stated events, the present paper focuses on the analysis of modifications in haematocrit, blood viscosity and erythrocyte deformability in Thoroughbred horses caused by two different levels of effort (6 to 9 m/s and 13 to 16 m/s), in the same track they train in and with their own jockeys. The...
Pulmonary response to airway instillation of autologous blood in horses. Exercise-induced pulmonary haemorrhage (EIPH) occurs in the majority of horses performing strenuous exercise. Associated pulmonary lesions include alveolar and airway wall fibrosis, which may enhance the severity of EIPH. Further work is required to understand the pulmonary response to blood in the equine airways. Objective: To confirm that a single instillation of autologous blood into horse airways is associated with alveolar wall fibrosis, and to determine if blood in the airways is also associated with peribronchiolar fibrosis. Methods: Paired regions of each lung were inoculated with bloo...
Evidence-based respiratory medicine in horses. It is clear from a review of the current scientific literature that an evidence-based approach to medical treatment of equine respiratory disease can be applied, at least in the instance of common lower respiratory diseases. In particular, there is clear evidence for efficacious treatments for recurrent airway obstruction and exercise-induced pulmonary hemorrhage, and with the recognition of this evidence, these treatments should be the first to be considered by a practitioner when treating these conditions. The purpose of this article is not only to identify the existence of relevant high-qua...
Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in thoroughbred horses. During high intensity exercise, the very high pulmonary artery pressure (Ppa) experienced by Thoroughbred horses is considered a major factor in the aetiology of exercise-induced pulmonary haemorrhage (EIPH). Recently, endothelin-1 (ET-1), a potent vasoconstrictive hormone, has been found to increase Ppa in horses at rest via binding to its ET-1A receptor subtype. In addition, plasma concentrations of ET-1 are increased in horses during and after high intensity exercise. Objective: If ET-1 increases Ppa during exercise in the horse, administration of a specific ET-1A antagonist would decrease ...
Is improved high speed performance following frusemide administration due to diuresis-induced weight loss or reduced severity of exercise-induced pulmonary haemorrhage? Prerace administration of frusemide to horses has been linked with a significant improvement in racing performance, but the basis for this improvement is unclear. Objective: To test whether improved performance with prerace administration of frusemide is due to the drug's diuresis-induced weight loss rather than its apparent alleviation of exercise-induced pulmonary haemorrhage (EIPH). Methods: Eight thoroughbred horses underwent 3 trials in a random order, 2 or 3 weeks apart: control (C), frusemide/unburdened (FU), and frusemide/burdened (FB). None of the horses were known to have exhibited p...
Evaluation of race distance, track surface and season of the year on exercise-induced pulmonary haemorrhage in flat racing thoroughbreds in Brazil. To our knowledge no studies evaluating risk factors to EIPH have been undertaken with such a population of horses in Brazil, which is one of the few countries in the racing community to accept the use of frusemide (FUR) as a prerace medication for bleeders. We also compared national results with those already in the literature. Objective: To verify the influence of variables such as distance of the race, racetrack surface, going and season of the year in the recurrence and severity of EIPH and its effect on the finishing position of flat racing Thoroughbreds in Brazil. Methods: 2118 post race ...
The effect of inspired gas density on pulmonary artery transmural pressure and exercise induced pulmonary haemorrhage. Pulmonary capillary stress failure, largely as a result of high pulmonary vascular pressures, has been implicated in the aetiology of EIPH. However, the role of the respiratory system in determining the magnitude of EIPH has received little attention. Objective: Horses breathing a gas of greater density than air will exhibit greater transmural pulmonary arterial pressures (TPAP) and more severe EIPH, and horses breathing a gas of lower density than air will exhibit lower TPAP and less severe EIPH, both compared with horses breathing air. Methods: Following a warm-up, 8 Thoroughbred horses were...