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.     

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.     

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.     

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.     

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.     

Pulmonary vascular pressures of strenuously exercising Thoroughbreds during intravenous infusion of nitroglycerin

OBJECTIVE: To determine whether intravenous infusion of nitroglycerin would modify pulmonary arterial, capillary, or venous hypertension in strenuously exercising Thoroughbreds. ANIMALS: 5 healthy Thoroughbred horses. PROCEDURE: Right atrial, right ventricular, and pulmonary vascular pressures were measured. Each horse was used in a control treatment (not medicated) and a nitroglycerin infusion (20 microg/kg of body weight/min) at rest and during exercise on a treadmill. Sequence of treatments was randomized for each horse, and treatments were separated by a 7-day interval. Galloping at 14.2 m/s on a 5% uphill grade elicited maximal heart rate (mean +/- SEM, 212 +/- 2 beats/min) and could not be sustained for > 90 seconds. Nitroglycerin dosage was selected, because maximal pulmonary and systemic hemodynamic effects of i.v. nitroglycerin were elicited at 5 microg/kg/min and increasing the dosage to 20 microg/kg/min did not cause adverse effects. RESULTS: In the control treatment, exercise performed at maximal heart rate resulted in a significant increase in right atrial as well as pulmonary arterial, capillary, and wedge pressures. Nitroglycerin infusion in standing horses significantly decreased right atrial and pulmonary vascular pressures, whereas heart rate increased. Exercise in nitroglycerin-infused horses also resulted in a significant increase in right atrial as well as pulmonary arterial, capillary, and wedge pressures, and these values were not significantly different from data for the control treatment. All horses experienced exercise-induced pulmonary hemorrhage for both treatments. CONCLUSIONS AND CLINICAL RELEVANCE: I.v. administration of nitroglycerin does not modify exercise-induced pulmonary hypertension and is unlikely to affect the incidence or severity of exercise-induced pulmonary hemorrhage in Thoroughbreds.     

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.     

Ureteral ligation prevents the haemodynamic effect of frusemide in pentobarbitol anaesthetised horses

Frusemide reduces pulmonary vascular pressures in resting horses and attenuates exercise-induced increases in these pressures in exercising horses. The mechanism underlying these effects of frusemide is unclear. We tested the hypothesis that the haemodynamic effects of frusemide are dependent on diuresis by examining the effect of frusemide in anaesthetised horses in which diuresis was prevented by ligation of ureters. Twenty four horses were assigned randomly to one of 4 treatments: 1) frusemide (1 mg/kg bwt i.v.) and intact ureters; 2) frusemide and ligated ureters; 3) saline placebo and ligated ureters; and 4) frusemide and phenylbutazone (4.4 mg/kg bwt i.v. 12 h and 15 min before frusemide) and ligated ureters. Frusemide administration to anaesthetised horses with intact ureters increased plasma total protein concentration and reduced mean right atrial, pulmonary artery and aortic pressures. There was no significant effect of frusemide administration on haemodynamic variables or plasma total protein concentration in horses with ligated ureters. The combination of frusemide and phenylbutazone increased mean right atrial, pulmonary artery and aortic pressures in horses with ligated ureters. This study demonstrates that, in anaesthetised horses, the haemodynamic effect of frusemide is dependent upon diuresis. We interpret these results as providing further evidence that the haemodynamic effect of frusemide in horses is attributable to a reduction in plasma and blood volume.     

Pulmonary artery and aortic pressure changes during high intensity treadmill exercise in the horse: effect of frusemide and phentolamine.

Intravenous frusemide (1.0 mg/kg bwt) or phentolamine (0.33 mg/kg bwt) was given to 7 horses 1 h before exercise and their effects on pulmonary artery and aortic pressure changes during strenuous exercise were examined. Short-term near-maximal treadmill exercise (10 m/sec, 3 degrees incline) produced increases in heart rate, mean pulmonary artery pressure (PAP), mean aortic pressure (AP), and packed cell volume (PCV). Frusemide did not affect heart rate, PAP or PCV during exercise. Frusemide significantly decreased mean AP by 10 to 15 mmHg during exercise. Phentolamine produced an increase in heart rate relative to control only early in exercise but not during later, more strenuous, exercise. Phentolamine had no statistically significant effect on AP, PAP, or PCV, but a significant reduction was observed between 180 and 230 sec of exercise when PAP and AP were standardised against heart rate. Frusemide did not prevent horses from haemorrhaging during exercise in this study. Treatment with phentolamine did not sufficiently reduce the PAP and AP to test our hypothesis that a reduction in PAP and AP would eliminate EIPH.     

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.     

Do Thoroughbred and Standardbred horses have similar increases in pulmonary vascular pressures during exertion?

To test the hypothesis that the pulmonary vascular pressures of Thoroughbred and Standardbred horses behave similarly during exertion. Measurements were made on 5 Thoroughbred and 5 Standardbred horses on a treadmill at rest and during 3-minute exercise intervals at speeds predicted to produce 75%, 90%, and 100% maximal heart rate. Left forelimb acceleration, heart rate, esophageal pressure, and pulmonary artery pressure were measured continuously. Pulmonary capillary and wedge pressures were measured during intermittent occlusion of the pulmonary artery. Breathing rate and gait frequency were the fundamental frequencies of the esophageal pressure and limb acceleration signals respectively. The ratio of speed:gait frequency gave stride length. The effects of exertion and breed were evaluated using two-way analysis of variance. Exertion produced significant increases in pulmonary artery (P = 0.001), capillary (P= 0.002), and wedge (P= 0.005) pressures. No significant effect of breed was detected on pulmonary artery pressure, but at exertion pulmonary capillary and wedge pressures were 15% (P= 0.03) and 23% (P= 0.04) greater in Thoroughbreds, respectively. Treadmill speed was ~12% greater (P= 0.04), stride length was ~25% greater (P= 0.0003), gait frequency was ~10% less (P= 0.006), breathing rate was ~10% less (P= 0.001), and heart rate was ~6% less (P= 0.06) for Thoroughbreds. There was no effect of breed on inspiratory or expiratory esophageal pressure although mean esophageal pressure was ~2 mmHg greater (P= 0.03) in exercising Standardbreds. In conclusion, pulmonary capillary and wedge pressures are greater in Thoroughbreds than in Standardbreds at similar fractions of maximal heart rate. This is compatible with the higher incidence of exercise-induced pulmonary hemorrhage observed in Thoroughbreds.     

Attenuation by phenylbutazone of the renal effects and excretion of frusemide in horses.

The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide without phenylbutazone led to diuresis, natriuresis, kaliuresis and chloruresis, and altered the ratio of sodium:chloride excretion from 0.4 to 1.0 in the first hour of diuresis. When frusemide and phenylbutazone were administered, sodium and chloride excretion in the first hour were significantly (P<0.05) reduced by 40 and 32%, respectively, when compared to frusemide administrationwithout phenylbutazone. The fractional clearance of sodium and chloride was also significantly reduced. Potassium excretion, potassium fractional clearance and the ratio of sodium to chloride excretion were not affected by administration of phenylbutazone. During peak diuresis, phenylbutazone did not affect the efficiency of frusemide with respect to electrolyte excretion. The plasma disposition of frusemide was not affected by phenylbutazone. However, the renal excretion of frusemide decreased by approximately 25%. We conclude that the decreased urinary excretion of frusemide by phenylbutazone led to an attenuation of frusemide-induced increases in urinary excretion of sodium and chloride. Since the efficiency of frusemide was not affected by phenylbutazone, we conclude that phenylbutazone attenuates the renal excretion of frusemide without inhibiting the intrarenal activity of frusemide in horses.     

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.     

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.     

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.     

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.     

Influence of cyclooxygenase inhibitors on furosemide-induced hemodynamic effects during exercise in horses.

Furosemide, which commonly is used as a prophylactic treatment for exercise-induced pulmonary hemorrhage in horses, may mediate hemodynamic changes during exercise by altering prostaglandin metabolism. To determine if furosemide's hemodynamic effects during exercise in horses could be reversed, cyclooxygenase inhibitors were administered with furosemide. Four treatments were administered 4 hours prior to treadmill exercise at 9 and 13 m/s. They included a control treatment (10 ml of 0.9% NaCl solution, IV), furosemide (1 mg/kg of body weight, IV) administered alone, and furosemide in combination with phenylbutazone (4 mg/kg, IV, q 12 h for 2 days) or with flunixin meglumine (1.1 mg/kg, IV, on the day of experiment). Five horses were randomly assigned to complete all treatments. Physiologic variables at rest prior to exercise were not influenced by treatments. Furosemide, administered alone, reduced mean right atrial pressure and mean pulmonary artery pressure during exercise. The combinations of furosemide and flunixin meglumine or furosemide and phenylbutazone, at both levels of exercise intensity, returned mean right atrial pressure and mean pulmonary artery pressure to the value of the control treatment. During rest and exercise, plasma lactate concentration, PCV, heart rate, mean carotid artery pressure, oxygen consumption, carbon dioxide elimination, and cardiac output were not altered by any of the treatments. At 5 minutes after exercise, the administration of furosemide, alone or with phenylbutazone, reduced mean right atrial pressure. Other measured variables were not significantly influenced by treatments during recovery from exercise. These results suggested that cyclooxygenase inhibition partially reverses the decrease in mean right atrial pressure or pulmonary artery pressure induced by furosemide during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horses

The possibility that pre-exercise inhalation of a bronchodilator by healthy horses could improve their mechanics of breathing and enhance performance was investigated. Ipratropium bromide (0.35 microg/kg bwt; n = 7) was administered by nebulisation 30 min before exercise and frusemide (1 mg/kg bwt; n = 6) was given in the same manner 2 h before exercise. Albuterol sulphate (360 and 720 microg; n = 7) were administered with a metered dose inhaler 2 h before exercise. Each drug was investigated independently of the others using cross-over protocols. Horses completed incremental exercise tests and oxygen consumption, carbon dioxide production, arterial blood gases, heart rate and measures of breathing mechanics including total pulmonary resistance (RL) and nasopharyngeal resistance (RU) were determined for each exercise intensity. The resistance of the lower airways was calculated subsequently from the difference between RL and RU. None of the drugs tested had an effect on any of the variables measured, possibly because maximal bronchodilation is stimulated in healthy horses by the normal sympathoadrenergic response to exercise. Therefore, the pre-exercise inhalation of a bronchodilator by a healthy horse is unlikely to improve performance capacity.     

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.