Relationship of pulmonary arterial pressure to pulmonary haemorrhage in exercising horses

Exercise-induced pulmonary haemorrhage (EIPH) is characterised by blood in the airways after strenuous exercise and results from stress failure of the pulmonary capillaries. The purpose of this experiment was to establish a threshold value of transmural pulmonary arterial pressure at which haemorrhage occurs in the exercising horse. Five geldings, age 4-14 years, were run in random order once every 2 weeks at 1 of 4 speeds (9, 11, 13, 15 m/s); one day with no run was used as a control. Heart rate, pulmonary arterial pressure and oesophageal pressure were recorded for the duration of the run. Transmural pulmonary arterial pressure was estimated by electronic subtraction of the oesophageal pressure from the intravascular pulmonary arterial pressure. Within 1 h of the run, bronchoalveolar lavage was performed and the red and white blood cells in the fluid were quantified. Red cell counts in the lavage fluid from horses running at 9, 11 and 13 m/s were not significantly different from the control value, but after runs at 15 m/s, red cell counts were significantly (P<0.05) higher. White cell counts were not different from control values at any speed. Analysis of red cell count vs. transmural pulmonary arterial pressure indicated that haemorrhage occurs at approximately 95 mmHg. Red cell lysis in the lavage fluid was also apparent at transmural pulmonary arterial pressures above 90 mmHg. We conclude that, in the exercising horse, a pulmonary arterial pressure threshold exists above which haemorrhage occurs, and that pressure is often exceeded during high speed sprint exercise.     

Clenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horses

The present study was carried out to ascertain whether beta2-adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 pg/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, right heart/pulmonary vascular pressures were determined at rest, sub-maximal exercise and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate and induced EIPH in all horses. In the control experiments, incremental exercise resulted in progressive significant increments in right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures and all horses experienced EIPH. Clenbuterol administration to standing horses caused tachycardia, but significant changes in mean right atrial or pulmonary vascular pressures were not observed. During exercise performed after clenbuterol administration, heart rate as well as right atrial and pulmonary arterial, capillary and wedge pressures also increased progressively with increasing work intensity. However, these values were not found to be statistically significantly different from corresponding data in the control study and the incidence of EIPH remained unaffected. Since clenbuterol administration also does not affect the transpulmonary pressure during exercise, it is unlikely that the transmural force exerted onto the blood-gas barrier of exercising horses is altered following i.v. clenbuterol administration at the recommended dosage.     

Review of furosemide in horse racing: its effects and regulation

Furosemide has been used empirically and has been legally approved for many years by the US racing industry for the control of exercise-induced pulmonary haemorrhage (EIPH) or bleeding. Its use in horses for this purpose is highly controversial and has been criticized by organizations outside and inside of the racing industry. This review concentrates on its renal and extra-renal actions and the possible relationship of these actions to the modification of EIPH and changes in performance of horses. The existing literature references suggest that furosemide has the potential of increasing performance in horses without significantly changing the bleeding status. The pulmonary capillary transmural pressure in the exercising horse is estimated to be over 100 mmHg. The pressure reduction produced by the administration of furosemide is not of sufficient magnitude to reduce transmural pressures within the capillaries to a level where pressures resulting in rupture of the capillaries, and thus haemorrhage, would be completely prevented. This is substantiated by clinical observations that the administration of furosemide to horses with EIPH may reduce haemorrhage but does not completely stop it. The unanswered question is whether the improvement of racing times which have been shown in a number of studies are due to the reduction in bleeding or to other actions of furosemide. This review also discusses the difficulties encountered in furosemide regulation, in view of its diuretic actions and potential for the reduction in the ability of forensic laboratories to detect drugs and medications administered to a horse within days or hours before a race. Interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and furosemide have also been examined, and the results suggest that the effects of prior administration of NSAID may partially mitigate the renal and extra-renal effects which may contribute to the effects of furosemide on EIPH.     

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. VIII. Conclusions and implications

This paper reviews a series of clinical, post mortem and imaging studies on exercise-induced pulmonary haemorrhage (EIPH) performed on 26 Thoroughbred racehorses. Post mortem techniques included routine gross, subgross and histological examination; coloured latex perfusions of pulmonary and bronchial circulations; and microradiography and computerised tomography scans of lungs with contrast injected vasculature. The major lesions were multiple, separate and coalescing foci of moderately proliferative small airway disease accompanied by intense neovascularisation of the bronchial circulation. As a result of bronchial artery angiogenesis, the systemic circulation dominated the vascular supply of the air exchange structures in affected areas, producing an apparent left to right shunt. Extensive areas of sequestered haemosiderophages indicated previous haemorrhage from vessels apparently supplied by the bronchial arteries. Diffuse and focal parenchymal destruction and connective tissue reactions in affected areas were considered to be secondary to localised haemorrhage and macrophage-induced damage. The aetiology of EIPH was not determined, but the multifocal, small airway-centred lesions indicated that low grade bronchiolitis, possibly of viral origin, was a factor. Gravitational effects also appear to contribute to dorsal distribution of the lesions. The mild focal and subclinical lesions confined to secondary lobules are thought to evolve into the serious lung pathology observed in EIPH cases through the effects of localised hypoxia induced by maximal exercise and partial airway obstruction. Once initiated, a vicious cycle of increasing inflammatory damage and further local bleeding is set in motion.     

Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of frusemide in strenuously exercising thoroughbred horses

The present study was carried out to examine whether pentoxifylline administration to horses premedicated with frusemide would attenuate the exercise-induced pulmonary arterial, capillary and venous hypertension to a greater extent than frusemide alone, thereby affecting the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Using established techniques, we determined right heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at rest and during exercise performed at maximal heart rate at a workload of 14 m/s on 3.5% uphill grade in the control (no medications), frusemide (250 mg i.v., 4 h pre-exercise)-control, and the frusemide (250 mg i.v., 4 h pre-exercise) + pentoxifylline (8.5 mg/kg bwt i.v., 15 min preexercise) treatments. Sequence of the 3 treatments was randomised for every horse and 7 days were allowed between them. In the control study, galloping at 14 m/s on 3.5% uphill grade elicited significant right atrial as well as pulmonary arterial, capillary and venous hypertension and all horses experienced EIPH as detected by the presence of fresh blood in the trachea on endoscopic examination. Frusemide administration was not attended by changes in heart rate at rest or during exercise. Although in the frusemide-control experiments, a significant reduction in mean pulmonary arterial, capillary and wedge pressures was observed both at rest and during galloping at 14 m/s on 3.5% uphill grade, all horses still experienced EIPH. Pentoxifylline administration to standing horses premedicated with frusemide caused nervousness, muscular fasciculations, sweating and tachycardia. Although these symptoms had largely abated within 15 min, there were no significant changes in the right atrial or pulmonary vascular pressures. Exercise in the frusemide + pentoxifylline experiments also caused significant right atrial as well as pulmonary arterial, capillary and venous hypertension, but these data were not found to be significantly different from the frusemide-control experiments. All horses in the frusemide + pentoxifylline experiments also experienced EIPH. In conclusion, our data indicate that pentoxifylline (8.5 mg/kg bwt i.v., 15 min pre-exercise) is ineffective in modifying the pulmonary haemodynamic effects of frusemide in exercising horses. It should be noted, however, that we did not examine whether erythrocyte plasticity was altered by the administration of pentoxifylline. Since the intravascular force exerted onto the blood-gas barrier of exercising horses premedicated with frusemide remained unaffected by pentoxifylline administration, it is concluded that concomitant pentoxifylline administration is unlikely to offer additional benefit to horses experiencing EIPH.     

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. IV. Changes in the bronchial circulation demonstrated by C.T. scanning and microradiography

The purpose of this study was to use radiographic contrast techniques and special imaging methods to identify and high-light bronchial arterial involvement in lung lesions associated with exercise-induced pulmonary haemorrhage (EIPH) in horses. The lungs from four horses with histories of EIPH were prepared for computerised tomographic scanning and microradiography by perfusing the broncho-oesophageal artery with a mixture of red latex and either barium or iodine contrast materials while the pulmonary supply received only blue latex. Computerised tomographic scan slices of the prepared inflated lungs were obtained from the caudal tip of the lung to the hilus. Microradiography of selected lung slices was also performed on a Faxitron. Diffuse areas of increased density, with preferential bronchial arterial supply noted on the computerised tomographic scans were confirmed by microradiography. Dense focal and diffuse plexuses of markedly hypertrophied and highly branched bronchial arterial networks were identified, centred around certain small airways. The vascular supply to these plexuses was recruited predominantly from neighbouring bronchial vessels, and in some cases, from the enlarged vasa vasorum of pulmonary arteries sending anastomoses to the affected areas. The authors conclude that bronchial vascular lesions in EIPH cases are the likely origin of haemorrhage; that small airway disease is the probable initiating stimulus for bronchial vascular proliferation in these lesions; and that the morphology and nature of the neovascular tissue in these lesions provides the conditions leading to haemorrhage in the lungs of horses with EIPH.     

Sex variation in the prevalence of exercise-induced pulmonary haemorrhage in racing quarter horses

Post race endoscopy was carried out on 255 two-year-old quarter horses and exercise-induced pulmonary haemorrhage (EIPH) was diagnosed in 166 (65 per cent) of them. Visible epistaxis was seen in a higher proportion of geldings than in either mares or stallions. The prevalence of EIPH was similar in mares (73 per cent) and in geldings (74 per cent). A significantly lower prevalence (49 per cent) was noted in stallions (P less than 0.01). It was concluded that a sex variation in the prevalence of EIPH exists in two-year-old quarter horses.     

Review of exercise induced pulmonary haemorrhage and its possible relationship with mechanical stress

Exercise induced pulmonary haemorrhage (EIPH) is a condition of uncertain aetiology. This article reviews the evidence relating to its incidence, clinical findings, radiological observations, histopathology and certain aspects of respiratory physiology. It is proposed that EIPH is primarily caused by mechanical stress in the dorsocaudal region of the lung.     

Inclined running increases pulmonary haemorrhage in the Thoroughbred horse

REASONS FOR PERFORMING STUDY: Capillary stress failure-induced (exercise-induced) pulmonary haemorrhage (EIPH) during intense running in horses is thought to involve both intravascular (i.e. mean pulmonary arterial pressure [Ppa] > 100 mmHg) and extravascular (e.g. negative inspiratory pressure swings) mechanisms. HYPOTHESIS: That inclined running would reduce breathing frequency (coupled to stride frequency) and increase tidal volume thus increasing lung volume changes and intrapleural pressure swings resulting in more pronounced EIPH. METHODS: Six Thoroughbred horses were run to volitional fatigue (incremental step test) on a level (L) and inclined (I; 10%) treadmill in random order. Pulmonary minute ventilation, arterial blood gases and mean Ppa were obtained during each run while EIPH severity was quantified via bronchoalveolar lavage (BAL) 30 mins post run. RESULTS: Time to fatigue did not differ between trials (P > 0.05). At end-exercise, breathing frequency was reduced (L, 127.8 +/- 3.0; I, 122.6 +/- 2.1 breaths/min; P < 0.05) and tidal volume increased (L, 11.5 +/- 0.6; I, 13.1 +/- 0.5 L; P < 0.05) during inclined running. No differences existed in end-exercise plasma [lactate] between trials (L, 24.5 +/- 2.9; I, 26.2 +/- 3.4 mmol/l, P > 0.05); however, the mean peak Ppa was reduced during the inclined run (L, 105+5; I, 96 +/- 4 mmHg, P < 0.05). In the face of reduced Ppa, EIPH severity was increased significantly (P < 0.05) during the inclined vs. level run (L, 37.0 +/- 11.7; I, 49.6 +/- 17.0 x 10(6) red blood cells/ml BAL fluid). CONCLUSIONS: Although inclined running lowered peak Ppa, EIPH severity was increased. It is likely that this effect resulted, in part, from an altered ventilatory pattern (i.e. increased tidal volumes and associated intrapleural pressure changes). POTENTIAL RELEVANCE: This conclusion supports an important role for extravascular factors in the aetiology of EIPH.     

Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide

The frusemide dose-response for attenuation of exercise-induced pulmonary capillary hypertension was studied in 7 healthy, exercise-conditioned Thoroughbred horses using previously described haemodynamic procedures. Four different doses of frusemide were tested: 250 mg regardless of bodyweight (amounting to 0.56 +/- 0.03 mg/kg bwt), 1.0 mg/kg bwt, 1.5 mg/kg bwt and 2.0 mg/kg bwt. Frusemide was administered i.v., 4 h before exercise. Haemodynamic data were obtained at rest and during treadmill exercise performed at 14.2 m/s on a 3.5% uphill grade; this workload elicited maximal heart rate of horses. Airway endoscopy was performed post exercise to detect exercise-induced pulmonary haemorrhage (EIPH). In standing horses, frusemide administration resulted in a significant (P<0.05) decrease in mean pulmonary arterial, pulmonary capillary and pulmonary artery wedge pressures, but significant differences among the various frusemide doses were not observed. In the control experiments, exercise caused significant increments in the right atrial as well as pulmonary arterial, wedge, and capillary pressures, and all horses experienced EIPH. Following frusemide administration, the exercise-induced rise in right atrial and pulmonary vascular pressures was significantly attenuated, but significant differences between the frusemide doses of 250 mg, 1.0 mg/kg, and 1.5 mg/kg were not discerned and all horses remained positive for EIPH. Although a further significant (P<0.05) attenuation of the exercise-induced rise in pulmonary capillary blood pressure occurred when frusemide dose increased from 250 mg to 2.0 mg/kg bwt, all horses still experienced EIPH. It is concluded that a linear response to increasing frusemide dosage in terms of attenuation of the pulmonary capillary hypertension does not exist in strenuously exercising Thoroughbred horses.     

A review of the pathophysiology of exercise-induced pulmonary haemorrhage in the equine athlete

In the United States, more than 75% of equine athletes are reported to suffer from exercise-related haemorrhage of the respiratory tract (Voynick and Sweeney, 1986; Sweeney et al., 1990). Fiberoptic endoscopy has traced the source of blood to beyond the bifurcation of the trachea. In 1981, the term exercise-induced pulmonary haemorrhage (EIPH) was introduced (Pascoe et al., 1981). Racehorses of all breeds, polo ponies and three-day event horses of mixed heritage, even foxhunters, may bleed (Voynick and Sweeney, 1986; Pascoe et al., 1981; Sweeney and Soma, 1983; Hillidge, 1986). Any horse working at speeds greater than 240 m/min is at risk (Voynick and Sweeney, 1986).The impact of exercise-induced pulmonary haemorrhage is difficult to assess. Most attempts to demonstrate statistically a negative correlation between EIPH and performance have been unrewarding, largely due to the number of uncontrollable variables (Pascoe et al., 1981; Raphel and Soma, 1982). In racing thoroughbreds (Mason et al., 1983) and standard breeds (MacNamara et al., 1990) approximately half as many EIPH-positive as EIPH-negative horses were placed in their races. Based on extensive intrapulmonary haemorrhage, a 3-year prospective study of sudden deaths in exercising thoroughbreds concluded that 9 out of 11 deaths were attributable to EIPH (Gunson et al., 1988).By correlation of clinical signs, thoracic radiographs, ventilation/perfusion scintigraphy, gross and subgross pathology and histopathology in 26 affected thoroughbreds, EIPH has been associated with chronic small airway inflammation, proliferation of subpleural, peribronchial and septal bronchial arterioles, interstitial connective tissue fibrosis and alveolar septal disruption in the dorsocaudal lung lobes (O'Callaghan et al., 1987). From this work it was proposed that the initial insult of EIPH started as focal, dorsocaudal pulmonary peribronchial inflammation which resulted in bronchial arterial neovascularization. Haemorrhage then occurred when, during exercise, bronchial blood pressure increased in fragile capillary buds. The incidence of bronchitis/bronchiolitis, regardless of aetiology, has been estimated to be 30% in non-racing equine athletes and close to 100% in one group of racing thoroughbreds (Sweeney et al., 1989). Histological study of lungs from horses with mild, moderate and severe chronic small airway disease consistently revealed a greater density of lesions in the diaphragmatic lobes (Winder and von Fellenberg, 1988).To understand further the aetiology and/or pathophysiology of EIPH, we will first explore some aspects of general mammalian and specific equine pulmonary and bronchial vascular anatomy and physiology. Exercise-related changes in these systems in normal and EIPH-positive horses will be briefly reviewed. Finally, a look at the types of therapies applied to bleeders may shed further light on the subject.     

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 promising biomarker for EIPH in racehorses.     

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. I. Clinical profile of horses

Detailed physical and clinical examinations were performed on 26 Thoroughbred racehorses which were used subsequently in a series of studies to investigate the contribution of the pulmonary and bronchial arterial circulations to the pathophysiology of exercise-induced pulmonary haemorrhage (EIPH). Twenty-five of the horses had been retired from race training in Hong Kong during the 1984-85 season, all but four raced that season; one horse had been retired the previous season. The average number of races for the group that season was 4.1 +/- 2 with an average distance of 1502 +/- 216 metres, mean racing speed 15.5 +/- 0.5 metres/sec. Time from last race to necropsy was 177 +/- 155 days, range 12 to 572 days. All but one horse had a known history of either EIPH or epistaxis. Time from last recorded incident of expistaxis (17 horses) to necropsy was 156 +/- 141 days, range 12 to 513 days, with a longer interval since last recorded endoscopic observation of EIPH. Focal abnormal lung sounds were detected in the dorsocaudal lungfields on auscultation during rebreathing in three horses and six had tracheobronchial cytology consistent with previous episodes of pulmonary haemorrhage (haemosiderophages). No other characteristics which might have allowed separation of this group of horses from other Thoroughbred horses recently in race training were identified.     

Exercise-induced pulmonary haemorrhage in the horses: results of a detailed clinical, post mortem and imaging study. VII. Ventilation/perfusion scintigraphy in horses with EIPH

Detailed post mortem examination of the lungs of horses with exercise-induced pulmonary haemorrhage (EIPH) has demonstrated significant small airway disease and intense bronchial arterial proliferation in the dorsocaudal lungfields. The purpose of this study was to investigate ventilation and perfusion distribution in the lungs of a similar group of horses to compare changes in the live animal with the previously reported post mortem findings. Thoracic radiography and ventilation/perfusion (V/Q) scintigraphy were performed on five racing Thoroughbreds with recent histories of EIPH. Parametric images of V/Q ratios for left and right lungfields were also generated from the scan images. In all horses, ventilation and perfusion deficits were demonstrated in the dorsocaudal areas of the lung corresponding closely to the observed radiographic lesions. In particular, the perfusion images and V/Q ratio displays indicated that, in affected areas of lung, pulmonary arterial perfusion was the more seriously impaired. This finding appears to confirm the post mortem evidence of reduced pulmonary arterial perfusion and bronchial arterial dominance in these areas. Ventilation deficits in the same areas also confirmed the likelihood of partial airway obstruction consistent with the small airway disease noted in previous post mortem observations. These results suggest that the vascular and airway lesions demonstrated in detailed post mortems of horses with EIPH are also functionally important in affected horses, even at rest. As a consequence of the apparent persistent, insidious and progressive nature of the lesions associated with EIPH there are serious long term implications for management of the condition.     

Effects of an external nasal strip and frusemide on pulmonary haemorrhage in Thoroughbreds following high-intensity exercise.

The purpose of this study was to examine the effects of an external nasal strip (NS), frusemide (FR) and a combination of the 2 treatments (NS + FR) on exercise-induced pulmonary haemorrhage (EIPH) in Thoroughbred horses. It was hypothesised that both the NS and FR would attenuate EIPH as assessed by red blood cell count in bronchoalveolar lavage fluid. In random order, 8 horses completed each of 4 sprint exercise tests on a treadmill: 1) NS; 2) FR (0.5 mg/kg bwt i.v., 4 h pre-exercise); 3) NS + FR; and 4) control (C; no treatment). After a 5 min warm-up (4.5 m/s), horses completed 2 min running at 120% maximum oxygen consumption (VO2max) with the treadmill set at 3 degrees incline. Mean +/- s.d. running speed was 14.2+/-0.2 m/s. In the FR and NS + FR trials, horses carried weight equal to that lost as a result of frusemide administration. During exercise at 120% Vo2max, oxygen consumption (Vo2) and carbon dioxide production (Vco2) were measured at 15 s intervals. Plasma lactate concentration was measured in samples collected before exercise, at the end of the sprint and after 5 min cool-down at the trot. Thirty minutes after the run, bronchoalveolar lavage (BAL) was performed and the red cell count in the fluid quantified. Vo2 and Vco2 were significantly lower in NS and NS + FR trials than in the C and FR trials at the end of the sprint exercise protocol. However, plasma lactate concentrations did not differ among treatments. Compared with the C trial (61.1+/-30.5 x 10(6) red blood cells/ml BAL fluid), pulmonary haemorrhage was significantly (P<0.05) decreased in both the NS (15.9+/-4.0 x 106 RBC/ml) and FR (12.2+/-5.8 x 10(6) RBC/ml) trials. EIPH in the NS + FR trial (7.9+/-1.0 x 10(6) RBC/ml) was further diminished (P<0.05) compared to the NS trial, but not different from the FR trial. We conclude that both the external nasal strip and frusemide attenuate pulmonary haemorrhage in Thoroughbred horses during high-speed sprint exercise. The external nasal strip appears to lower the metabolic cost of supramaximal exertion in horses. Given the purported ergogenic effects of frusemide, the external nasal strip is a valuable alternative for the attenuation of EIPH.     

Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses

The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre-exercise)-control, and furosemide (250 mg i.v., 4 h pre-exercise)+clenbuterol (0.8 microg/kg i.v., 11 min pre-exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub-maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide-control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide-control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood-gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH.     

Oxidant injury,nitric oxide and pulmonary vascular function: implications for the exercising horse

The athletic ability of the horse is facilitated by vital physiological adaptations to high-intensity exercise, including a thin (but strong) pulmonary blood-gas barrier, a large pulmonary functional reserve capacity and a consequent maximum oxygen uptake (VO2max) far higher than in other species. A high pulmonary artery pressure also serves to enhance pulmonary function, although stress failure of lung capillaries at high pulmonary transmural pressures, and the contribution of other factors which act in the exercising horse to increase pulmonary vascular tone, may lead to pathological or pathophysiological sequelae, such as exercise-induced pulmonary haemorrhage (EIPH). Reactive oxygen species (ROS) are an important component of the mammalian inflammatory response. They are released during tissue injury and form a necessary component of cellular defences against pathogens and disease processes. The effects of ROS are normally limited or neutralized by a multifactorial system of antioxidant defences, although excessive production and/or deficient antioxidant defences may expose healthy tissue to oxidant damage. In the lung, ROS can damage pulmonary structures both directly and by initiating the release of other inflammatory mediators, including proteases and eicosanoids. Vascular endothelial cells are particularly susceptible to ROS-induced oxidant injury in the lung, and both the destruction of the pulmonary blood-gas barrier and the action of vasoactive substances will increase pulmonary vascular resistance. Moreover, ROS can degrade endothelium-derived nitric oxide (NO), a major pulmonary vasodilator, thereby, with exercise, synergistically increasing the likelihood of stress failure of pulmonary capillaries, a contributing factor to EIPH. This review considers the implications for the exercising horse of oxidant injury, pulmonary vascular function and NO and the contribution of these factors to the pathogenesis of equine respiratory diseases.     

Intravenous pentoxifylline does not affect the exercise-induced pulmonary arterial, capillary or venous hypertension in Thoroughbred horses

The present study was carried out to examine whether intravenously administered pentoxifylline-a phosphodiesterase inhibitor which increases red blood cell deformability and decreases blood viscosity-would attenuate the magnitude of exercise-induced pulmonary capillary hypertension in healthy, fit Thoroughbred horses and in turn, diminish the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. Hemodynamic data were collected at rest, and during exercise performed at 8 and 14 m/sec on 3.5% uphill grade in the control (no medications) and the pentoxifylline (8.5 mg/kg, i.v.) experiments. The sequence of treatments was randomized for every horse and 7 days were allowed between treatments. Galloping at 14 m/sec on 3.5% uphill grade elicited maximal heart rate. In both treatments, simultaneous measurements of phasic and mean right atrial and pulmonary arterial, capillary and wedge pressures were made using catheter-tip-manometers whose signals were carefully referenced at the point of the left shoulder. In the control study, exercise resulted in progressive significant increments in heart rate, right atrial and pulmonary arterial, capillary and venous pressures; thereby, confirming that exercising Thoroughbreds develop significant pulmonary hypertension. All horses experienced exercise-induced pulmonary hemorrhage (EIPH) in the control experiments. Pentoxifylline administration to standing horses caused anxiety, tachycardia, muscular fasciculations/tremors and mild sweating, but statistically significant changes in right atrial and pulmonary arterial, capillary and venous pressures were not detected. Exercise in the pentoxifylline treatment also resulted in progressive significant increments in heart rate and right atrial as well as pulmonary vascular pressures, but these data were not statistically significantly different from those in the control study and the incidence of EIPH remained unchanged. Thus, it was concluded that i.v. pentoxifylline is ineffective in attenuating the exercise-induced pulmonary arterial, capillary and venous hypertension in healthy, fit Thoroughbred horses.     

Epistaxis related to exercise-induced pulmonary haemorrhage in south African Thoroughbreds

This study investigated if environmental factors had an effect on the incidence of epistaxis related to exercise-induced pulmonary haemorrhage (EIPH) among racehorses in southern Africa. Data covering the period 1986-2001 and involving 778 532 race runs were analysed. This included the following information: date of race, age, sex, name of breeder, trainer, distance, jockey, state of going, weight carried, racing centre and altitude. Veterinarians employed by the Jockey Club suspended officially entered horses that presented with epistaxis (frank bleeding from the nostrils) after racing. On-course endoscopy is not performed as a standard practice at any southern African racetrack. Epistaxis was identified in 1287 horses (0.165%). More horses presented with EIPH-related epistaxis (a) at sea level, (b) from May to October, (c) when older (> 3 years), (d) after 1995, (e) on Fridays and Sundays, and (f) more in geldings than in mares or entire males. No association could be established between epistaxis and breeder, trainer, distance run, jockey, state of going and weight carried. It is concluded that the frequency of EIPH-related epistaxis is associated with altitude, winter and spring, sex and age. It is suggested that racing at lower altitudes may increase the probability of exercise-induced pulmonary haemorrhage.