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.     

Effects of furosemide on the racing times of Thoroughbreds

The effects of furosemide on the racing times of 79 horses without exercise-induced pulmonary hemorrhage (EIPH) and 52 horses with EIPH were investigated. Racing times were adjusted to 1-mile equivalent racing times by 2 speed handicapping methods, and analysis of covariance was used to adjust actual racing times by winning time and distance for each race. All 3 methods of determining racing time indicated that geldings without EIPH had significantly faster racing times (P less than 0.05) when given furosemide before racing than when furosemide was not given before racing. Females and colts without EIPH were determined to have faster racing times when furosemide was given before racing, but the difference was not significant. Geldings with EIPH had significantly faster racing times (P = 0.0231) when given furosemide before racing, as determined by one of the speed handicapping methods. There was a strong correlation (range 0.9314 to 0.9751) between the 1-mile equivalent racing times, as determined by the 2 speed handicapping methods for horses with and without EIPH. Furosemide failed to prevent the development of EIPH in many horses that were previously considered to be EIPH-negative. When given furosemide, 62 (25.3%) of 235 EIPH-negative horses were EIPH-positive after racing. Furosemide had questionable efficacy for prevention of EIPH in known EIPH-positive horses. Thirty-two (61.5%) of 52 EIPH-positive horses given furosemide before a race remained EIPH-positive after that race.     

Exercise-induced pulmonary hemorrhage in exercising Thoroughbreds: preliminary results with pre-exercise medication

Thoroughbreds with a confirmed history of exercise-induced pulmonary hemorrhage (EIPH) were treated pre-exercise with atropine sulfate, cromolyn, ipratropium or furosemide. Atropine prevented EIPH in 3 of 3 trials in 1 horse, while having no significant effect on bleeding status in the other 2 horses. Pre-exercise treatment with cromolyn had no significant effects in the 3 horses. Pre-exercise treatment of ipratropium was apparently responsible for preventing EIPH in 17 out of 18 trials in 2 horses. The pharmacologic properties of ipratropium in the horse have not been studied, but based on human investigation it seems most probable that its bronchodilator effects are responsible for preventing EIPH in the 2 horses. Furosemide administered in different dosages and time intervals prior to exercise did not prevent EIPH in these 3 horses.     

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.     

Association between exercise-induced pulmonary hemorrhage and performance in Thoroughbred racehorses

OBJECTIVE: To determine whether exercise-induced pulmonary hemorrhage (EIPH) was associated with racing performance inThoroughbred horses not medicated with furosemide and not using nasal dilator strips. DESIGN: Observational cross-sectional study. ANIMALS: 744 two- to 10-year-old Thoroughbred horses racing in Melbourne, Australia. PROCEDURE: Horses were enrolled prior to racing, and a tracheobronchoscopic examination was performed after 1 race. Examinations were recorded on videotape, and presence and severity (grade 0 to 4) of EIPH were subsequently determined by 3 observers blinded to the horses' identity. Race records were abstracted for each horse examined. RESULTS: Overall, 52.1% of horses eligible for participation in the study were examined, and horses that were examined did not differ from horses that were not examined in regard to age, sex distribution, or proportion of horses that won or finished in the first 3 positions. Horses with EIPH grades < 1 were 4.0 times as likely to win, 1.8 times as likely to finish in the first 3 positions, and 3.03 times as likely to be in the 90th percentile or higher for race earnings as were horses with grades > 2. Horses with EIPH grades > 1 finished significantly farther behind the winner than did horses without EIPH. However, odds that horses with grade 1 EIPH would win or finish in the first 3 positions were not significantly different from odds for horses without EIPH. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that EIPH is associated with impaired performance in Thoroughbred racehorses not medicated with furosemide and not using nasal dilator strips.     

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.     

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.     

Pharmacology of Furosemide in the Horse: A Review

Furosemide, a diuretic, is frequently administered to horses for the prophylaxis of exercise-induced pulmonary hemorrhage and the treatment of a number of clinical conditions, including acute renal failure and congestive heart failure. Furosemide increases the rate of urinary sodium, chloride, and hydrogen ion excretion. Plasma potassium concentration decreases after furosemide administration but urinary potassium excretion in horses is minimally affected. Renal blood flow increases after furosemide administration. Systemically, furosemide increases venous compliance and decreases right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and pulmonary blood volume. The systemic hemodynamic effects of furosemide are only manifest in the presence of a functional kidney, but can occur in the absence of diuresis, emphasizing the importance of the renal-dependent extra-renal effects of furosemide. The renal and systemic hemodynamic effects of furosemide are modified by prior administration of nonsteroidal anti-inflammatory drugs. Furosemide administration attenuates exercise-induced increases in right atrial, aortic, and pulmonary artery pressures in ponies. Furosemide prevents exercise and allergen-induced bronchoconstriction in humans and decreases total pulmonary resistance in ponies with recurrent obstructive airway disease. These pharmacologic effects are frequently used to rationalize its questionable efficacy in the prevention of exercise-induced pulmonary hemorrhage. Neither the effect of furosemide on athletic performance nor its efficacy in the prevention of exercise-induced pulmonary hemorrhage has been convincingly demonstrated.     

Physiologic effects of furosemide in combination with water restriction when administered at 4 and 24 hours prior to high-intensity treadmill training

Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design. Blood samples were collected for determination of furosemide, lactate, hemoglobin, blood gas, and electrolyte concentrations. Heart rate and pulmonary arterial pressure were measured throughout the run and endoscopic examination and bronchoalveolar lavage (BAL) performed. Horses were assigned an EIPH score and the number of red blood cells in BAL fluid determined. Although not significantly different, endoscopic EIPH scores were lower in the 4-hr versus the 24-hr and saline groups. RBC counts were not significantly different between the treatment groups. Pulmonary arterial pressures were significantly increased at higher speeds; however, there were no significant differences between dose groups when controlling for speed. A small sample size and unknown bleeding history warrant a larger-scale study.     

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.     

Monitoring furosemide in racehorses participating in an EIPH program

Analytical procedures were developed to monitor furosemide concentrations in post-race serum and urine samples obtained from horses participating in an exercise-induced pulmonary haemorrhage (EIPH) program. High performance liquid chromatography with ultraviolet light detection proved a reliable, sensitive method for measuring urinary furosemide concentrations up to 12 h after administration of either 150 or 250 mg of the drug to race horses. However, this method was unreliable for determination of serum furosemide concentration. High performance liquid chromatography with fluorescence detection proved a reliable, sensitive method for measuring serum furosemide concentrations in horses administered 250 mg of the diuretic, permitting detection approximately 5–10 ng/ml 6 h after treatment. This method was applied field conditions where furosemide was administered to horses (between 150 and 250 mg intravenously) 4 h prior to the race. Analytical results assisted establishing a threshold concentration of 85 ng/ml for serum furosemide. was found that serum furosemide concentrations are a valid measure of compliance with furosemide administration in the EIPH program.     

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.     

Radiographic aspects of exercise-induced pulmonary hemorrhage in racing horses

Abnormal pulmonary radiopacities were identified in 13 racing horses in which a diagnosis of exercise-induced pulmonary hemorrhage (EIPH) had been confirmed. The lesions were in the caudal lung lobe in all horses; seven were on the right and three on the left, and the laterality for three could not be determined. In ten horses the opacities, which were large and peripherally located, obliterated the thoracophrenic angle. They merged with the silhouette of the diaphragm and had a circular or ovoid surface directed toward the hilum. The intensity of opacification of the consolidated areas varied, and they often were not sharply marginated. Dorsal displacement of the pulmonary arteries was noted in the region of the radiopacity in seven horses. Varying volumes of pleural effusion were observed in nine horses. Serial radiographic examinations were performed in seven horses. The pulmonary radiopacities cleared within ten days in two horses. In the remaining five horses, gradual resolution, characterized by a reduction in lesion size with improved margination, occurred during several months. The central region of the radiopaque lesion commonly had a patchy appearance, suggesting cavitation. Normal pulmonary vascular and interstitial markings were evident following complete resolution of these lesions. The cause of these abnormal pulmonary opacities has not been determined. Pathologic-radiologic correlations will be required to improve understanding of the pathophysiology of EIPH in the racing horse.     

Effects of furosemide on the racing times of horses with exercise-induced pulmonary hemorrhage

In 3 groups of horses with exercise-induced pulmonary hemorrhage (EIPH), comparisons of racing times and finishing positions were made between the 5 races before the horses were given furosemide and 5 races after furosemide administration. The horses were grouped according to 3 methods used to diagnose EIPH: group 1, observation of hemorrhage at the nostrils within 1 hour after a workout or race; group 2, observation of pulmonary hemorrhage only by endoscopic examination after a race or workout; and group 3, observation of hemorrhage at the nostrils during a race or immediately after a race. Group 4 horses were randomly selected horses running during the study period and were not given furosemide. The statistical method was analysis of covariance and the dependent variable was horses' time per distance. The study compared the 4 groups of horses, using the estimated value of the horses (less than or equal to +10,000 or greater than +10,000), and the horses' interaction in races 1 through 5 before and races 6 through 10 after furosemide treatment. The horses' times were adjusted by the relevant covariates, distance, track variant, and winning time per distance. Significant changes in horses' time per distance were not noticed when comparing values from races 1 through 5 with those in races 6 through 10 in group 1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary vascular pressures of thoroughbred horses exercised 1, 2, 3 and 4 h after furosemide administration

Furosemide premedication of horses 4 h prior to exercise significantly attenuates exercise-induced pulmonary capillary hypertension which may help diminish the severity of exercise-induced pulmonary haemorrhage. As pulmonary hemodynamic effects of furosemide may be mediated via a reduction in plasma volume (which is most pronounced 15-30 min postfurosemide administration, with plasma volume recovering thereafter), we hypothesized that administration of furosemide at intervals shorter than 4 h before exertion may be more effective in attenuating the exercise-induced rise in pulmonary capillary blood pressure. Thus, our objective was to determine whether furosemide-induced attenuation of exercise-induced pulmonary arterial, capillary and venous hypertension would be enhanced when the drug is administered at intervals shorter than 4 h before exercise. Using established techniques, right atrial, and pulmonary arterial, capillary and wedge (venous) pressures were ascertained in seven healthy, sound, exercise-trained Thoroughbred horses in a randomized split-plot experimental design. Measurements were made at rest and during exercise performed at maximal heart rate (217 +/- 3 beats/min) in the control (no medications) experiments and following furosemide administration (250 mg intravenously (i.v.)) at 1, 2, 3 and 4 h before exercise. Sequence of treatments was randomized and 7 days were allowed between experiments on each horse. Although furosemide administration in the four treatment groups caused only insignificant changes in the pulmonary arterial, capillary and wedge pressures of standing horses, furosemide-induced reduction in mean right atrial pressure achieved statistical significance in the 2 h postfurosemide experiments. In the control studies, exercise was attended by statistically significant increments in mean right atrial, as well as pulmonary arterial, capillary and wedge pressures. Although exercise in each of the four furosemide experiments was also attended by significant increments in right atrial as well as pulmonary vascular pressures, in the 1, 2 and 3 h postfurosemide experiments, mean right atrial pressure increased to a significantly lower value than in the control study. Exercise-induced changes in pulmonary vascular pressures in the 1 h postfurosemide experiments were not different from the pressures in the control study. There was a significant attenuation of exercise-induced pulmonary capillary and venous hypertension in the 2, 3 and 4 h postfurosemide experiments, but significant differences among these treatments were not found. Thus, these data did not support the contention that administration of furosemide at intervals shorter than 4 h before exercise is more effective in attenuating exercise-induced pulmonary capillary or venous hypertension in Thoroughbred horses.     

Efficacy of furosemide in the treatment of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses

The repeatability of endoscopic observations of exercise-induced pulmonary hemorrhage (EIPH) and the efficacy of furosemide as a prophylactic treatment of horses with EIPH were studied in Thoroughbred race horses after consecutive breezes (at or near maximum speed, approx 16 m/s). Of 56 horses examined greater than or equal to 2 times, 21 (38%) had identical EIPH scores, whereas 26 (46%) and 9 (16%) had scores that differed by greater than or equal to 1 grade. In 56 nontreated horses, there was good agreement between 2 consecutive observations (K = 0.59, Z = 4.54, P less than 0.001). Similar comparisons after placebo (saline solution) treatment of 21 horses yielded fair to good agreement, whereas poorer agreement was seen after furosemide treatment of 23 horses. Comparison of average and maximum EIPH scores of 44 horses with a minimum of 4 observations (2 nontreated, 1 saline-treated, and 1 furosemide-treated) indicated that although furosemide did not stop EIPH, it did reduce the EIPH score in 28 (64%) horses.     

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.     

Bronchoalveolar lavage findings in horses with exercise intolerance.

Significant differences were detected by bronchoalveolar lavage (BAL) between horses racing successfully and those showing exercise intolerance. Neutrophil percentage, haemosiderophage percentage and total bacterial numbers were significantly elevated in horses with exercise intolerance. BAL provided a more accurate indication of the incidence and extent of exercise induced pulmonary haemorrhage (EIPH) than visual inspection.     

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.