Hyperhydration prior to a simulated second day of the 3-day moderate intensity equestrian competition does not cause arterial hypoxemia in Thoroughbred horses.

Dehydration and the associated impairment of cardiovascular and thermoregulatory function comprise major veterinary problems in horses performing prolonged exercise, particularly under hot and humid conditions. For these reasons, there is considerable interest in using pre-exercise hyperhydration to help maintain blood volume in the face of the excessive fluid loss associated with sweat production during prolonged exertion. However, recently it was reported that pre-exercise hyperhydration causes arterial hypoxemia in horses performing moderate intensity exercise simulating the second day of an equestrian 3-day event competition (E3DEC) which may adversely affect performance (Sosa Leon et al. in Equine Vet J Suppl 34:425-429, 2002). These findings are contrary to data from horses performing short-term maximal exertion, wherein hyperhydration did not affect arterial O2 tension/saturation. Thus, our objective in the present study was to examine the impact of pre-exercise hyperhydration on arterial oxygenation of Thoroughbred horses performing an exercise test simulating the second day of an E3DEC. Control and hyperhydration studies were carried out on seven healthy Thoroughbred horses in random order, 7 days apart. In the control study, horses received no medications. In the hyperhydration experiments, nasogastric administration of NaCl (0.425 g/kg) 5 h pre-exercise induced a plasma volume expansion of 10.9% at the initiation of exercise. This methodology for inducing hypervolemia was different from that of Sosa Leon et al. (2002). Blood-gas tensions/pH as well as plasma protein, hemoglobin and blood lactate concentrations were measured pre-exercise and during the exercise test. Our data revealed that pre-exercise hyperhydration neither adversely affected arterial O2 tension nor hemoglobin-O2 saturation at any time during the exercise test simulating the second day of an E3DEC. Further, it was observed that arterial blood CO2 tension, pH, and blood lactate concentrations also were not affected by pre-exercise hyperhydration. However, hemodilution in hyperhydrated horses caused an attenuation of the expansion in the arterial to mixed-venous blood O2 content gradient during phases B and D of the exercise protocol, which was likely offset by an increase in cardiac output. It is concluded that pre-exercise hyperhydration of horses induced in the manner described above is not detrimental to arterial oxygenation of horses performing an exercise test simulating the second day of an E3DEC.

Nitric oxide synthase inhibition in thoroughbred horses augments O2 extraction at rest and submaximal exercise, but not during short-term maximal exercise.

REASON FOR PERFORMING STUDY: Work is required to establish the role of endogenous nitric oxide (NO) in metabolism of resting and exercising horses. OBJECTIVES: To examine the effects of NO synthase inhibition on O2 extraction and anaerobic metabolism at rest, and during submaximal and maximal exertion. METHODS: Placebo and NO synthase inhibition (with Nomega-nitro-L-arginine methyl ester [L-NAME] administered at 20 mg/kg bwt i.v.) studies were performed in random order, 7 days apart on 7 healthy, exercise-trained Thoroughbred horses at rest and during incremental exercise leading to 120 sec of maximal exertion at 14 m/sec on a 3.5% uphill grade. RESULTS: At rest, NO synthase inhibition significantly augmented the arterial to mixed-venous blood O2 content gradient and O2 extraction as mixed-venous blood O2 tension and saturation decreased significantly. While NO synthase inhibition did not affect arterial blood-gas tensions in exercising horses, the exercise-induced increment in haemoglobin concentration and arterial O2 content was attenuated. In the L-NAME study, during submaximal exercise, mixed-venous blood O2 tension and haemoglobin-O2 saturation decreased to a greater extent causing O2 extraction to increase significantly. During maximal exertion, arterial hypoxaemia, desaturation of haemoglobin and hypercapnia of a similar magnitude developed in both treatments. Also, the changes in mixed-venous blood O2 tension and haemoglobin-O2 saturation, arterial to mixed-venous blood O2 content gradient, O2 extraction and markers of anaerobic metabolism (lactate and ammonia production, and metabolic acidosis) were not different from those in the placebo study. CONCLUSION: Endogenous NO production augments O2 extraction at rest and during submaximal exertion, but not the during short-term maximal exercise. Also, NO synthase inhibition does not affect anaerobic metabolism at rest or during exertion. POTENTIAL RELEVANCE: It is unlikely that endogenous NO release modifies aerobic or anaerobic metabolism in horses performing short-term maximal exertion.

Pre-exercise hypervolaemia is not detrimental to arterial oxygenation of horses performing a prolonged exercise protocol simulating the second day of a 3-day equestrian event.

REASONS FOR PERFORMING STUDY: Hyperhydration, prior to prolonged moderate-intensity exercise simulating the 2nd day of a 3-day equestrian event (E3DEC), may induce arterial hypoxaemia detrimental to performance. OBJECTIVES: Because moderate-intensity exercise does not induce arterial hypoxaemia in healthy horses, the effects of pre-exercise hypervolaemia on arterial oxygenation were examined during a prolonged exercise protocol. METHODS: Blood-gas studies were carried out on 7 healthy, exercise-trained Thoroughbred horses in control and hyperhydration experiments. The study conformed to a randomised crossover design. The sequence of treatments was randomised for each horse and 7 days were allowed between studies. Hyperhydration was induced by administering 0.425 g/kg bwt NaCl via nasogastric tube followed by free access to water. The exercise protocol was carried out on a treadmill set at a 3% uphill grade and consisted of walking at 2 m/sec for 2 min, trotting for 10 min at 3.7 m/sec, galloping for 2 min at 14 m/sec (which elicited maximal heart rate), trotting for 20 min at 3.7 m/sec, walking for 10 min at 1.8 m/sec, cantering for 8 min at 9.2 m/sec, trotting for 1 min at 5 m/sec and walking for 5 min at 2 m/sec. RESULTS: NaCl administration induced a significant mean +/- s.e. 15.5 +/- 1.1% increase in plasma volume as indicated by a significant reduction in plasma protein concentration. In either treatment, whereas arterial hypoxaemia was not observed during periods of submaximal exercise, short-term maximal exertion caused significant arterial hypoxaemia, desaturation of haemoglobin, hypercapnoea, and acidosis in both treatments. However, the magnitude of exercise-induced arterial hypoxaemia, desaturation of haemoglobin, hypercapnoea, and acidosis in both treatments remained similar, and statistically significant differences between treatments could not be demonstrated. CONCLUSIONS: It was concluded that significant pre-exercise expansion of plasma volume by this method does not adversely affect the arterial oxygenation of horses performing a prolonged exercise protocol simulating the 2nd day of an E3DEC.

Inhibition of nitric oxide synthase with L-NAME does not increase lactate production at rest or during short-term high-intensity exercise in Thoroughbred horses.

The present study was carried out to determine whether inhibition of nitric oxide (NO) synthase promotes anaerobic metabolism in exercising horses, resulting in a significantly increased blood lactate concentration. N(omega)-nitro-L-arginine methyl ester (L-NAME) is a potent inhibitor of NO synthase that has been tested in horses and other species. Two sets of experiments, namely placebo (saline control) and L-NAME (20 mg/kg, i.v.) studies, were carried out on seven healthy, sound, exercise-trained, Thoroughbred horses in random order, 6 to 7 days apart. In both experiments, an incremental exercise protocol was used and data were obtained at rest, during submaximal exercise performed at 8 m/s on a 4.5% uphill grade, and during galloping at 14 m/s on a 4.5% uphill grade--a workload that not only elicited maximal heart rate and induced exercise-induced pulmonary haemorrhage, but also could not be sustained for more than 90 s. Measurements were also made in the recovery period. Mixed-venous blood samples, obtained at matched intervals in the two sets of experiments, were analysed in triplicate for determining the lactate concentration. Following administration of L-NAME, significant bradycardia occurred at rest (27 +/- 1 vs 37 +/- 2 beats/min in the placebo trials; p<0.0001) as well as during submaximal exercise (183 +/- 4 vs 200 +/- 4 beats/min in the placebo trials; p<0.001), but the heart rate increased during galloping at 14 m/s on a 4.5% uphill grade to reach values observed in the placebo trials (215 +/- 2 beats/min) and significant differences were not found. At rest, the mixed-venous blood lactate concentration was similar in the two experiments. With exercise, the mixed-venous blood lactate concentration increased progressively as work intensity increased in both trials, but significant differences were not found between the placebo and the L-NAME experiments during submaximal exercise, near-maximal exercise or recovery. These experiments demonstrated that inhibition of NO synthase in Thoroughbred horses does not promote enhanced anaerobic metabolism at rest or during short-term incremental exercise leading to galloping at maximal heart rate.

Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses.

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, L-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O(2) content (Ca(O(2))) increased to significantly lower values. These data suggest that, whereas L-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher workloads.

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.

Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses.

Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pulmonary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was carried out to examine whether the structural changes in the blood-gas barrier caused by a prior bout of high-intensity short-term exercise capable of inducing EIPH would affect the arterial hypoxemia induced during a successive bout of exercise performed at the same workload. Two sets of experiments, double- and single-exercise-bout experiments, were carried out on seven healthy, sound Thoroughbred horses. Experiments were carried out in random order, 7 days apart. In the double-exercise experiments, horses performed two successive bouts (each lasting 120 s) of galloping at 14 m/s on a 3.5% uphill grade, separated by an interval of 6 min. Exertion at this workload induced arterial hypoxemia within 30 s of the onset of galloping as well as desaturation of Hb, a progressive rise in arterial PCO2, and acidosis as exercise duration increased from 30 to 120 s. In the single-exercise-bout experiments, blood-gas/pH data resembled those from the first run of the double-exercise experiments, and all horses experienced EIPH. Thus, in the double-exercise experiments, before the horses performed the second bout of galloping at 14 m/s on a 3.5% uphill grade, stress failure of pulmonary capillaries had occurred. Although arterial hypoxemia developed during the second run, arterial PO2 values were significantly (P < 0.01) higher than in the first run. Thus prior exercise not only failed to accentuate the severity of arterial hypoxemia, it actually diminished the magnitude of exercise-induced arterial hypoxemia. The decreased severity of exercise-induced arterial hypoxemia in the second run was due to an associated increase in alveolar PO2, as arterial PCO2 was significantly lower than in the first run. Thus our data do not support a role for structural changes in the blood-gas barrier related to the stress failure of pulmonary capillaries in causing the exercise-induced arterial hypoxemia in horses.

Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds.

The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O2 content increased significantly with exercise in both treatments, while the mixed venous blood O2 content decreased as O2 extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.

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.

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.

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.

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.

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.

Pulmonary vascular resistance of horses decreases with moderate exercise and remains unchanged as workload is increased to maximal exercise.

This study was carried out to examine changes in pulmonary vascular resistance (PVR) induced by moderate and strenuous exercise; the objective being to understand why pulmonary artery blood pressure of exercising horses increases progressively as work intensity increases. Pulmonary arterial and wedge pressures (referenced at the point of the left shoulder) were determined simultaneously with cardiac output in 2 groups of healthy, sound, exercise-trained horses. Horses in Group 1 (n = 8) were studied at rest and during exercise performed at 8 and 13 m/s; the latter workload eliciting maximal heart rate (mean +/- s.e. 212 +/- 3 beats/min). Horses in Group 2 (n = 7 Thoroughbreds) were studied at rest and during galloping at 14.5 m/s on 5% uphill grade, a workload which elicited maximal heart rate (217 +/- 3 beats/min) and could not be sustained for > 90 s. Pulmonary vascular resistance was calculated by dividing pulmonary perfusion pressure gradient (i.e. mean pulmonary arterial pressure minus mean pulmonary wedge pressure) with cardiac output. Pulmonary arterial and wedge pressures, pulmonary perfusion pressure gradient and cardiac output increased significantly (P < 0.05) with exercise in both groups. There were no differences in PVR between the 2 groups of horses at rest. In Group 1 horses PVR decreased significantly (P < 0.05) with exercise at 8 m/s, but further pulmonary vasodilation did not occur as workload increased to 13 m/s. During exercise at 14.5 m/s on 5% grade, PVR of Group 2 horses also decreased significantly and was not different from values for 8 or 13 m/s in Group 1 horses. It is concluded that PVR reaches its nadir during moderate exercise, presumably due to upper limit of recruitment and distension having been reached. Therefore, in accordance with Ohm's law (P alpha Q x PVR), in going to higher workloads pulmonary blood flow (Q) remained the sole determinant of the rise in pulmonary arterial blood pressure (P). Our data also indicate that pulmonary artery wedge pressure is another variable that is important in determining the absolute value of pulmonary arterial blood pressure.

Repeated administration of frusemide does not offer an advantage over single dosing in attenuating exercise-induced pulmonary hypertension in thoroughbred horses.

The objective of the present study was to ascertain whether administration of a second dose of frusemide would attenuate exercise-induced pulmonary hypertension more than a single dose. Right atrial, right ventricular and pulmonary vascular pressures were determined in 7 healthy, sound, exercise-trained Thoroughbred horses at rest and during exercise (14.2 m/s + a 3.5% uphill grade) performed at maximal heart rate (217 +/- 3 beats/min [mean +/- s.e.]). Horses were studied during the following 3 treatments in random order 7 days apart: control (no medication), frusemide single dose (250 mg i.v. 4 h pre-exercise), and frusemide double dose (250 mg i.v., 4 h pre-exercise + 250 mg i.v. 2 h pre-exercise). In the control study, exercise resulted in significant (P < 0.05) right atrial as well as pulmonary arterial, capillary and venous hypertension. In the frusemide single dose experiments, a significant (P < 0.05) attenuation of the exercise-induced rise in right atrial and pulmonary vascular pressures was observed. However, compared with frusemide single dose experiments, significant changes in the exercise-induced right atrial and pulmonary arterial, capillary and venous hypertension were not observed in the frusemide double dose experiments. Therefore, it is concluded that administration of an additional dose of frusemide is unlikely to affect the severity of EIPH in racing Thoroughbred horses more than a single dose.

Regional distribution of blood flow in the brain of horses at rest and during exercise.

OBJECTIVE: To examine regional distribution of blood flow in the brain of horses at rest and during exercise. ANIMALS: 9 clinically normal horses. PROCEDURE: Regional brain blood flow was measured using radionuclide-labeled 15-microns-diameter microspheres injected into the left ventricle, while reference blood samples were obtained from the aorta. RESULTS: At rest, cerebral cortex and caudate nuclei received significantly higher blood flow, compared with cerebral white matter. A similar perfusion heterogeneity existed in the cerebellum. In the brain stem, a gradual tapering of blood flow from thalamus-hypothalamus towards medulla was observed in standing horses. Progressive significant increases in heart rate and in aortic and right atrial pressures occurred during exercise at 8 and 13 m/s, and horses developed significant arterial hypoxemia and hypercapnia. Cerebral and cerebellar gray- to white-matter perfusion heterogeneity was maintained during exercise, indicating differential metabolic O2 needs. Despite arterial hypoxemia, hypercapnia, and hypertension, exercise did not result in significant changes in blood flow to the cerebral cortex and caudate nuclei whereas, in cerebral white matter, a significant decrease in blood flow was observed. In all cerebral tissues, vascular resistance increased during exercise, indicating autoregulation of cerebral blood flow. In the cerebellar cortex, blood flow increased significantly with strenuous exercise as vasodilation occurred. Vascular resistance in cerebellar white matter increased during exercise at 13 m/s. Blood flow in the medulla, pons, midbrain, and thalamus-hypothalamus was not significantly altered during exercise from that at rest. CONCLUSION: Despite arterial hypoxemia, hypercapnia, and hypertension, autoregulation of cerebral and cerebellar blood flow is maintained in horses during exercise.

L-NAME does not affect exercise-induced pulmonary hypertension in thoroughbred horses.

The present study was carried out to examine the effects of nitric oxide synthase inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME) on the right atrial as well as on the pulmonary arterial, capillary, and venous blood pressures of horses during rest and exercise performed at maximal heart rate (HRmax). Experiments were carried out on seven healthy, sound, exercise-trained Thoroughbred horses. Using catheter-tip manometers, with signals referenced at the point of the shoulder, we determined phasic and mean right atrial and pulmonary vascular pressures in two sets of experiments [control (no medications) and L-NAME (20 mg/kg iv given 10 min before exercise studies)]. The studies were carried out in random order 7 days apart. Measurements were made at rest and during treadmill exercise performed on a 5% uphill grade at 6, 8, and 14.2 m/s. Exercise on a 5% uphill grade at 14.2 m/s elicited HRmax and could not be sustained for >90 s. In quietly standing horses, L-NAME administration caused a significant rise in right atrial, as well as pulmonary arterial, capillary, and venous pressures. This indicates that nitric oxide synthase inhibition modifies the basal pulmonary vasomotor tone. In both treatments, exercise caused progressive significant increments in right atrial and pulmonary vascular pressures, but the values recorded in the L-NAME study were not different from those in the control study. The extent of exercise-induced tachycardia was significantly decreased in the L-NAME study at 6 and 8 m/s but not at 14.2 m/s. Thus, L-NAME administration may not modify the equine pulmonary vascular tone during exercise at HRmax. However, as indicated by a significant reduction in heart rate, L-NAME seems to modify the sympathoneurohumoral response to submaximal exercise.

Pulmonary vascular pressures of strenuously exercising Thoroughbred horses after administration of phenylbutazone and frusemide.

The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days. Measurements were made at rest and during incremental exercise performed on a treadmill set at 3.5% uphill grade. In the frusemide control experiment, horses received frusemide 250 mg i.v., 4 h pre-exercise. In the phenylbutazone + frusemide experiment, horses received 4 i.v. injections of phenylbutazone (4.4 mg/kg bwt) at 12 h intervals. Twenty-four hours after the last phenylbutazone injection, horses received frusemide 250 mg i.v. and exercise was performed 4 h later. This latter regimen mimics prevailing veterinary practice at Illinois racetracks. The highest work intensity (14.2 m/s, 3.5% uphill grade) elicited maximal heart rate of horses. Significant right atrial, as well as pulmonary arterial, capillary and venous hypertension occurred with exertion in all 3 experiments. However, in the frusemide-control and the phenylbutazone + frusemide studies, the exercise induced rise in mean right atrial and pulmonary vascular pressures was significantly (P<0.05) attenuated in comparison with that in the control experiments. Statistically significant differences were not found between the frusemide control study and the phenylbutazone + frusemide study either at rest or during any level of exertion. Therefore, it was concluded that the phenylbutazone treatment in our study did not mitigate the pulmonary haemodynamic effects of frusemide in strenuously exercising Thoroughbred 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.

Evaluation of udder health and mastitis in llamas.

OBJECTIVE: To investigate intramammary infections in llamas, identify the pathogens responsible, and determine whether effects of intramammary infection could be detected by use of mastitis indicator tests commonly used for cows. DESIGN: Observational study. ANIMALS: 100 llamas on 10 farms. PROCEDURE: Milk samples were evaluated by bacterial culturing and by determination of somatic cell count (SCC), using direct microscopic and automated counting methods, California Mastitis Test score, pH, and N-acetyl-beta-d-glucosaminidase activity. Correlation coefficients were determined among the various mastitis indicator tests, and test results were determined for milk from infected and uninfected glands. RESULTS: Evidence of intramammary infection was evident in 76 of 369 (21%) milk samples, with 54 of 94 (57%) llamas having at least 1 infected gland. Staphylococcus sp other than Staphylococcus aureus were the predominant pathogens. None of the llamas had clinical signs of mastitis, and significant differences were not detected in SCC, California Mastitis Test score, pH, or N-acetyl-beta-d-glucosaminidase activity between infected and uninfected samples. California Mastitis Test scores were negative or trace for 307 of 313 (98%) samples, and SCC were low. In contrast, pH and N-acetyl-beta-d-glucosaminidase activity of milk from uninfected glands were higher than values reported for milk from uninfected cows, and neither variable was significantly correlated with the number of somatic cells in samples of llama milk. CLINICAL IMPLICATIONS: Although intramammary infections develop in llamas, inflammation (mastitis) appears to be rare. Values for mastitis indicator tests used for cows cannot be directly extrapolated to llamas. Subclinical mastitis is apparently not an important problem in llamas in the United States.