Exercise-induced pulmonary hemorrhage
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Exercise induced pulmonary hemorrhage (EIPH), also known as "bleeding" or a "bleeding attack", refers to the presence of blood in the airways of the lung in association with exercise. EIPH is common in horses undertaking intense exercise, but it has also been reported in human athletes, racing camels and racing greyhounds. Horses that experience EIPH may also be referred to as “bleeders” or as having “broken a blood vessel”. In the majority of cases EIPH is not apparent unless an endoscopic examination of the airways is performed following exercise. However, a small proportion of horses may show bleeding at the nostrils after exercise, which is known as epistaxis.
EIPH in Horses
EIPH has been reported to occur in a variety of race horse breeds including racing Thoroughbreds (both flat racing and steeplechasing or jump racing), American Quarter Horses (incidence of 50-75%), Standardbreds (incidence of 40-60%), Arabians, and Appaloosas. EIPH has also been reported in eventers, jumpers, polo ponies, endurance horses, draft horses that pull competitively, and horses taking part in Western speed events such as reining, cutting and barrel racing. EIPH is now considered to be an inevitable consequence of moderate to intense exercise in horses and other athletic animals. The lowest intensities of exercise which have been reported to cause EIPH are intense trotting (40-60% maximal oxygen uptake) and cantering at speeds of 16–19 miles per hour (26–31 km/h).
The affliction occurs when blood enters the air passages of a horse's lung, due to fractured lung capillaries. Blood is sometimes evident discharging from a horse's nostrils (epistaxis), however, epitaxis usually only occurs in 5% of bleeders. If a horse does not exhibit epistaxis but is suspected to have EIPH, an endoscopic exam is performed soon after the horse is exercised.
Exercise-induced pulmonary hemorrhage (EIPH), also known as "bleeding" or a "bleeding attack", refers to the presence of blood in the airways of the lung in association with exercise. EIPH often occurs in horses that race at high speeds. The number of horses with EIPH increases in proportion to speed and intensity. It is rare in endurance horses or draft breeds.(Hinchcliff & 2007 95) Sudden death in horse athletes can be caused by Exercise-induced pulmonary hemorrhage (EIPH).
Based on surveys of horses examined endoscopically following racing, around 40 to 70% of horses have been reported to have blood in the trachea following a single post-race examination. One of the more recent and larger studies found an overall prevalence of just under 60%. The time at which the examination is carried out can determine whether or not blood is seen. The usual time for examination is 30–40 minutes following exercise. If examination is carried out too soon after exercise then blood may not have progressed from the dorso-caudal (top and back) of the lung into the trachea. If the examination is carried out too long after exercise then any blood may have moved up the trachea and been swallowed and therefore not be visible at the time of examination. In one study (Birks et al. 2002), when horses were endoscoped on at least three separate occasions following racing, all horses had blood in the trachea on at least one occasion.
Epistaxis (blood coming from one or both nostrils) is much less common. In a survey of over 220,000 horse starts in UK Flat and National Hunt (jump) racing, 185 cases of epistaxis were identified giving a frequency of 0.83/1000 starts. Similar frequencies have been reported for epistaxis in Japan (1.5 per 1000 starts) and South Africa (1.65 per 1000 starts). However a study of racehorses in Korea reported a much higher frequency (8.4 per 1000 starts).
It is believed that nearly all horses experience EIPH when exposed to strenuous exercise, and it has the potential to decrease lung function over time. However, there are no documented cases of bleeding in wild horses when rounded up[unreliable source?] with helicopters from mountain tops in pens miles away.
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Epistaxis is diagnosed when blood is visible at either or both nostrils during or following exercise. To confirm whether the blood is from the upper or lower airway requires further examination by endoscopy, although in some cases it is not possible to determine the location. In the majority of epistaxis cases, the blood originates from the lung. Epistaxis during or following exercise can less commonly occur as a result of upper airway hemorrhage, for example following head trauma. Poor athletic performance, frequent swallowing and coughing in the immediate post-exercise recovery period may be suggestive of EIPH. But, a definitive diagnosis can only be made by endoscopic examination of the trachea. In the case where no blood is visible in the trachea, EIPH in the small airways may still be present and can be confirmed by a broncho-alveolar lavage.
- Endoscopy: EIPH is most commonly diagnosed by endoscopic examination of the trachea following exercise although a small proportion of horses will have blood at the nostrils (epistaxis) during or following intense exercise. Sometimes epistaxis may not be apparent until the horse has lowered its head, aiding drainage of the blood. In severe cases blood may be visible in the trachea immediately upon endoscopic examination soon after exercise. The most common current practice is to perform endoscopy of the trachea around 30–60 minutes after exercise. As the hemorrhage most commonly originates in the dorsal caudal (top-back) part of the lung it may not appear in the trachea immediately. With time it may travel to the trachea under the influence of mucociliary clearance, gravity and ventilation. Blood may be visible in the trachea for several days following a bout of intense exercise and moderate to severe EIPH. The amount of blood visible in the trachea at the time of examination is most commonly graded on a 0 (no blood) to 4 (airways awash with blood) scale.
- Bronchoalveolar lavage (BAL): If blood is not visible in the trachea, then examination of the smaller airways in the lung may reveal hemorrhage. In this procedure sedation is commonly used and the endoscope is advanced past the carina into the smaller bronchi. Local anaesthetic is usually instilled into the airways to reduce coughing. BAL is performed and if a horse has experienced EIPH then the fluid that is recovered can be observed to be pink or red in colour. This fluid can be submitted for cytopathogy and the number of red blood counted. Whereas scoring of the amount of blood during endoscopic examination of the trachea is semi-quantitative, quantitative counts of the numbers of red blood cells in BAL represent a quantitative estimate of the severity of EIPH. BAL red blood cell counts are more sensitive for detecting EIPH than is visualisation of blood in the trachea, but they may be less useful when severe hemorrhage has occurred, and it should also be borne in mind that they merely reflect the situation in the localized region of the lung which has been lavaged.
- Cytopathology: Even if blood is not visible in the airways, two types of cells that can be seen under cytological examination of either a tracheal wash or bronchoalveolar sample can indicate that EIPH has occurred. It may be possible to visualise red blood cells directly under a microscope. The number of red blood cells present can be quantified using a haemocytometer. While some red blood cells may be present in a lung wash sample, this is normally very low and in the order of less than 10 red blood cells/ul of fluid. In the case of EIPH, the numbers will be several magnitudes or more higher. The presence of high numbers of hemosiderophages also indicate that hemorrhage has occurred in the lung at some time in the past. Hemosiderophages are alveolar macrophages that have ingested and digested red blood cells from previous episodes of EIPH. The end product of the digestion of the red blood cells is an iron-storage complex known as hemosiderin.
- Radiography: Radiography of the chest to image the lungs has limited use in detecting either acute EIPH or damage to the lung as a result of repeated episodes of EIPH. The main benefit of taking chest radiographs as part of the clinical investigation of EIPH is to rule out other disease conditions.
- Pulmonary scintigraphy: Pulmonary scintigraphy may detect moderate to severe alterations in the perfusion and possibly ventilation of the dorso-caudal lung (O‘Callaghan et al., 1987). The use of radio-labelled red blood cells and scintigraphy to localise and or quantify hemorrhage is not useful due to general sequestration of labeled RBC by the lung, even in the absence of hemorrhage.
Lungs of horses that have experienced repeated episodes of EIPH show a characteristic blue-gray-brown staining when examined post mortem. The staining is due to the presence of haemosiderin. The staining is usually most intense in the dorso-caudal region of the left and right diaphragmatic lobes. There are often distinct borders between healthy lung tissue and those parts of the lungs that have been affected by EIPH.
A variety of different causes of EIPH have been proposed. These include high pulmonary vascular pressure, upper airway obstruction, mechanical trauma, lower airway obstruction, inflammation, abnormalities of blood coagulation, inhomogeneity of ventilation and locomotory trauma. To date most theories have been unable to explain why EIPH occurs in the dorso-caudal lung and the pattern of progression in a cranial direction.
High pulmonary blood pressures
The most widely accepted theory at present is that high transmural pressures lead to pulmonary capillary stress failure. Pulmonary capillary transmural pressure is determined by pulmonary capillary pressure and airway pressure. The horse has very high pulmonary vascular pressures during intense exercise; commonly exceeding 100mmHg in the pulmonary artery during intense exercise. During expiration the high positive pressures in the pulmonary blood vessels pushing out are opposed by high positive airway pressures pushing back and this does not place undue stress on the thin blood vessel walls. During inspiration the high positive pressures in the pulmonary blood vessels pushing out are met by negative pressures distending the blood vessel and placing increased stress on the walls. Studies in vitro have demonstrated that significant disruption of the pulmonary capillaries occurs at pressures of approximately 80 mmHg. In vivo it has also been shown that significant EIPH occurs above a mean pulmonary artery pressure of around 80-95 mmHg. On the basis of this theory, any factor or disease that would increase pulmonary vascular pressures (e.g. hypervolaemia) or increase the magnitude of the negative pressures in the lung during inspiration (e.g. dynamic upper airway obstruction) would be expected to increase the severity of EIPH. But neither experimentally induced laryngeal hemiplegia nor dorsal displacement of the soft palate increased pulmonary capillary transmural pressure. Furthermore, the magnitude of exercise-induced pulmonary arterial, capillary and venous hypertension is reportedly similar in horses either with or without EIPH.
Locomotory associated trauma
An alternative theory for EIPH is based on locomotory forces. The theory is based on the fact that during galloping, the absence of any bone attachment of the forelegs to the spine in the horse causes the shoulder to compress the cranial rib cage (Schroter et al. 1998). The compression of the chest initiates a pressure wave of compression and expansion which spreads outwards. However, due to the shape of the lung and reflections off the chest wall, the wave of expansion and compression becomes focussed and amplified in the dorso-caudal lung (Schroter et al. 1999). The alternate expansion and compression at the microscopic level in adjacent areas of lung tissue creates shear stress and capillary disruption. The theory predicts that hemorrhage would be more severe on hard track surfaces, but it does not explain why EIPH can occur in horses during swimming exercise.
A new proposal as to how high pulmonary venous pressures lead to the capillary rupture and the tissue changes observed has recently been proposed. Regional veno-occlusive remodeling, especially within the caudodorsal lung fields, contributes to the pathogenesis of EIPH, with the venous remodeling leading to regional vascular congestion and hemorrhage, hemosiderin accumulation, fibrosis, and bronchial angiogenesis. EIPH is most likely a multi-factorial condition involving airway, vascular, cardiac and locomotory components.
While all horses undertaking intense exercise experience some degree of EIPH, some horses consistently experience greater haemorrhage and other horses experience isolated episodes of increased EIPH. In the case of horses that consistently demonstrate greater severity of EIPH this is most likely due to congenital factors, such as very high pulmonary vascular pressures. In horses that experience isolated episodes of increased severity of EIPH, possible contributing factors may include, amongst others, pulmonary infection or atrial fibrillation.
Effects on Performance
Epistaxis has been shown to have a marked negative effect on performance. However the effects of endoscopically diagnosed EIPH on performance have been less clear, with conflicting studies reporting a negative, none, and in some cases a positive effect on performance. While single bouts of EIPH may not even be apparent to the rider, owner or trainer of a horse unless an endoscopic examination is undertaken, the effect on performance within a single race appears to be significant but relatively subtle. In a 2005 study, horses finishing races with grade 4 EIPH were on average 6 metres behind those finishing with grade 0. However, the effect of repeated bouts of EIPH that occur with daily training may lead to more significant changes and a greater degree of tissue damage over time with consequent loss of lung function.
Management and Treatment
A wide variety of treatments have been used or suggested for treatment of EIPH, including resting, anti-inflammatories (e.g. corticosteroids), bronchodilators, anti-hypertensive agents (including nitric oxide donors and phosphodiesterase inhibitors), conjugated estrogens (e.g. Premarin), antifibrinolytics (e.g. aminocaproic acid and tranexamic acid), snake venom, aspirin, vitamin K, bioflavinoids, diuretics (e.g. furosemide, known as Lasix or Salix), nasal strips (e.g. FLAIR Nasal Strips), concentrated equine serum and omega-3 fatty acids.
Both the diuretic furosemide and, to a much lesser extent, FLAIR Nasal Strips have been reported to reduce EIPH under laboratory and field conditions.
In two separate studies, the anticholinergic bronchodilator ipratropium bromide was demonstrated either to abolish or to significantly reduce endoscopically visible EIPH in horses which previously had bled consistently. Ipratropium inhibits bronchoconstriction and bronchial mucus secretion but it does not diffuse into the blood when administered by inhalation, so side-effects such as cardiovascular stimulation are not apparent. Further clinical investigation of its application in the management of EIPH would seem to be indicated.
A single study has shown that concentrated equine serum reduced EIPH, but there is currently no evidence to suggest that either rest, anti-inflammatory drugs, bioflavinoids, oestrogens, antifibrinolytics, aspirin, phosphodieterase inhibitors or surgical correction of upper airway obstructions are capable of doing so. In contrast, nitric oxide and aminocaproic acid have been shown to worsen EIPH.
Although furosemide (Lasix) has been used extensively to minimise EIPH, it is believed to be ineffective in 50% of cases. It has been reported to improve racing times in horses both with and without endoscopically visible EIPH, possibly due to a lowering of body weight as a consequence of its potent diuretic action. Less desirable side-effects of its chronic usage include hypokalemia and hypomagnesemia.
The use of Lasix in competing horses is prohibited in some countries and it is regarded as a banned substance by the International Olympic Committee.
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