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Departments of 1 Veterinary Biosciences and 2 Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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It is reported that preexercise hyperhydration caused arterial O2 tension of horses performing submaximal exercise to decrease further by 15 Torr (Sosa-Leon L, Hodgson DR, Evans DL, Ray SP, Carlson GP, and Rose RJ. Equine Vet J Suppl 34: 425-429, 2002). Because hydration status is important to optimal athletic performance and thermoregulation during exercise, the present study examined whether preexercise induction of hypervolemia would similarly accentuate the arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise. Two sets of experiments (namely, control and hypervolemia studies) were carried out on seven healthy, exercise-trained Thoroughbred horses in random order, 7 days apart. In resting horses, an 18.0 ± 1.8% increase in plasma volume was induced with NaCl (0.30-0.45 g/kg dissolved in 1,500 ml H2O) administered via a nasogastric tube, 285-290 min preexercise. Blood-gas and pH measurements as well as concentrations of plasma protein, hemoglobin, and blood lactate were determined at rest and during incremental exercise leading to maximal exertion (14 m/s on a 3.5% uphill grade) that induced pulmonary hemorrhage in all horses in both treatments. In both treatments, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, acidosis, and hyperthermia developed during maximal exercise, but statistically significant differences between treatments were not found. Thus preexercise 18% expansion of plasma volume failed to significantly affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing maximal exercise. Although blood lactate concentration and arterial pH were unaffected, hemodilution caused in this manner resulted in a significant (P < 0.01) attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O2 content gradient.
blood-gas tensions during exercise; hyperhydration; plasma volume; plasma protein concentration
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INTRODUCTION |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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EXERCISE-INDUCED ARTERIAL hypoxemia is routinely observed in strenuously exercising Thoroughbreds (1, 7, 18-21, 29, 30), and it has been reported that the occurrence of arterial hypoxemia limits athletic performance (5, 29). Although "relative" alveolar hypoventilation, as evidenced by the increasing arterial CO2 tension despite significantly increased alveolar ventilation during strenuous exercise, contributes to the observed reduction in arterial O2 tension, this mechanism does not account for the entire decrease in arterial O2 tension observed in exercising horses. Thus it is suggested that both diffusion limitation, probably related to the dramatic shortening of the pulmonary capillary transit time, as well as ventilation-perfusion inhomogeneity also play a role in bringing about exercise-induced arterial hypoxemia in horses (1, 5, 7, 18-21, 29, 30).
Simultaneous with the development of arterial hypoxemia, exercising
Thoroughbreds also exhibit significant pulmonary arterial, capillary,
and venous hypertension (14-17). The ensuing high
transmural pulmonary capillary pressure contributes to the stress
failure of pulmonary capillaries (2, 32), resulting in a
rather high incidence of exercise-induced pulmonary hemorrhage (EIPH;
Refs. 13, 28). Structural changes in the
blood-gas barrier associated with stress failure of pulmonary
capillaries (10) and exercise-induced arterial hypoxemia
are also observed in human subjects performing strenuous exertion
(4, 5, 9, 22, 23, 26, 33-35). These
observations have aroused considerable interest in determining the role
of structural changes in the blood-gas barrier (2, 10, 24,
32) in bringing about exercise-induced arterial hypoxemia. In
this context, although there have been several reports in human
subjects (4, 5, 9, 26, 33, 34) as well as in Thoroughbred
horses (7, 18-21) suggesting that exercise-induced arterial hypoxemia more likely has a functional basis, rather than a
structural basis, the issue is far from being completely settled.
Arguments against the structural basis for arterial hypoxemia in
galloping Thoroughbreds have been that 1) arterial hypoxemia develops rather quickly with onset of strenuous exercise (being well
developed at 30 s of high-intensity exercise) and that its severity does not change significantly with increasing exercise duration, even though structural changes in the blood-gas barrier are
expected to intensify with increasing exercise duration (7, 18-21); and 2) in healthy Thoroughbreds, during
a successive bout of short-term high-intensity exercise performed 6 min
after the first high-intensity exercise bout, an accentuation of
arterial hypoxemia could not be demonstrated (18). This is
similar to data reported from several laboratories studying human
subjects performing repeat bouts of exercise (4, 9, 26).
However, recently, it was reported (25) that preexercise
hyperhydration of Standardbred horses, leading to a significant
(~10.8%) expansion of the plasma volume at end exercise, caused mean
arterial O2 tension to decrease further by 15 Torr during
submaximal exercise performed at 55-61% maximal O2
consumption (
O2 max), and it was
suggested that by causing a more profound arterial hypoxemia during
moderate- to high-intensity exercise, hypervolemia may adversely affect
athletic performance of horses (25). The investigators
(25) concluded that "the most likely cause of the more
severe arterial hypoxemia in the hyperhydrated group during the intense
exercise phase was some degree of pulmonary edema, from the
extravasation of the administered fluid." Thus, despite considerable
interest, uncertainty exists as to the mechanism(s) responsible for
the exercise-induced arterial hypoxemia in performance horses. Although
interesting, these findings in hypervolemic Standardbred horses
(25) are in sharp contrast with observations in exercising human subjects wherein a significant expansion of plasma volume did not
significantly affect the arterial blood-gas tensions (35). Because hydration status is important to optimal athletic performance and thermoregulation during exercise, and because maximal exercise (wherein arterial hypoxemia is more commonly observed and is a known
factor in limiting athletic performance; Refs. 5,
29) was not examined in the previous study
(25), our primary objective in the present study was to
ascertain whether preexercise induction of significant hypervolemia
would accentuate the arterial hypoxemia observed during high-intensity
short-term exercise eliciting maximal heart rate and EIPH in
Thoroughbred racehorses. Toward this goal, we examined changes in
arterial blood-gas tensions in healthy, sound, exercise-trained
Thoroughbred horses performing an incremental exercise protocol leading
to galloping at maximal heart rate in the control and acute
hypervolemia (hyperhydration) studies, which were carried out in random
order, 7 days apart. Hypervolemia in our experiments was induced with
NaCl administration to horses via a nasogatric tube, 285-290 min preexercise.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Horses. Experiments were carried out on seven healthy, sound Thoroughbred horses (3 fillies, 4 geldings), 3-6 yr old, and weighing 459 ± 38 kg. They were exercise trained for a period of 7 wk before undertaking the blood-gas studies (7, 8, 18-21). The horses were housed in an air-conditioned building, and were accustomed to being handled by people. They were fed a diet of alfalfa hay and oats, and free access to water was provided. The horses were dewormed periodically and were inoculated with tetanus toxoid and strangles vaccine. Our protocols and procedures were approved by the Institutional Animal Care and Use Committees.
Exercise training. After the horses were familiarized with walking, trotting, cantering, and galloping on the high-speed treadmill for 1 wk, all horses were exercised 3 days/wk in the following manner with the treadmill set on the flat, i.e., 0% grade. Beginning with a walk at 2 m/s for 120 s, belt speed was increased at the rate of 1 m/s every 60 s until the horse had trotted at 6 m/s for 60 s. Treadmill speed was then raised to 8 m/s, and the horses were cantered for 60 s. Cantering was followed by galloping at 14 m/s for 120 s. Belt speed was then decreased, first to 5 m/s for 60 s and then to 2 m/s for 300 s before the treadmill was stopped. After initial exercise training for 4 wk in this manner, for the next 3 wk, this incremental exercise regimen was performed 3 days/wk with the treadmill set at a 3.5% uphill grade.
Work intensity eliciting EIPH. Because occurrence of EIPH in horses demonstrates that capillary stress failure and related structural changes in the blood-gas barrier have occurred (2, 32), for the present study we intended to use a workload capable of eliciting EIPH consistently. Trials to ascertain work intensity needed to elicit maximal heart rate and EIPH were undertaken on completion of the above-described exercise training. In agreement with previous work (7, 18-21), it was observed that galloping at 14 m/s on a 3.5% uphill grade not only elicited maximal heart rate but also induced EIPH in all horses as demonstrated by the presence of fresh blood in the trachea on postexercise airway endoscopic examination (13, 14, 28). It was also observed in these trials that our horses could not sustain galloping at 14 m/s on a 3.5% uphill grade for >120 s despite vigorous humane encouragement. Thus this workload, i.e., 14 m/s on a 3.5% uphill grade, was selected for further experimentation because it represented a strenuous effort eliciting maximal heart rate and EIPH in the experimental horses.
Experimental procedures. Our procedures for blood-gas and hemodynamic studies have been described in detail previously (14-21); therefore, only a brief description is given here. On the day of the study, after local anesthesia in the 17th intercostal space, the abdominal aorta was percutaneously catheterized. Thereafter, with the use of local infiltration of 2% lidocaine HCl, cardiac catheters (8-F) equipped with a tip manometer (Millar Instruments, Houston, TX), fluid-filled lumen, and a thermistor (Edward Laboratories, Santa Clara, CA) were advanced into the right ventricle and the pulmonary artery via introducers inserted into the left jugular vein. The locations of various catheters were confirmed by monitoring the characteristic phasic blood pressure waveforms on an oscillographic recorder. These catheters permitted simultaneous sampling of the aortic and pulmonary arterial (mixed venous) blood as well as continuous monitoring of the pulmonary arterial blood (core) temperature during the experiments. After catheter placement, horses stood quietly on the treadmill for ~45-50 min before blood-gas and pH studies were undertaken.
In the present study, changes in plasma protein concentration were used to assess the changes in plasma volume and hydration status (3). This is because the quantity of circulating plasma protein is constant in healthy animals, and, therefore, acute changes in plasma protein concentration are indicative of the changes in the plasma volume (3). Plasma protein concentration was determined by refractometry, and the percent change in plasma volume was calculated as [(PP1/PP2)
1.0] × 100, where PP1 and PP2
are the initial and the test plasma protein concentrations, respectively (3). Blood-gas tensions, pH, hemoglobin
concentration, hemoglobin O2 saturation, and O2
content were determined by using a carefully calibrated blood-gas
analyzer/CO-oximeter (ABL520 system, Radiometer, Copenhagen, Denmark),
and all blood-gas tensions and pH data were corrected to the
simultaneously measured pulmonary artery blood (core) temperature.
Mixed venous blood lactate concentration was determined as described
previously (7, 18, 21). In the present study,
O2 extraction (%) was calculated as (arterial-to-mixed venous blood O2 content gradient/arterial O2
content) × 100.
Experimental design and protocol. In the present study, all horses were studied in the control as well as the hypervolemia (hyperhydration) experiments, which were carried out in random order, 7 days apart. All experimentation was carried out in an air-conditioned laboratory, where the ambient temperature was maintained at 20-21°C.
Before these experiments were undertaken, separate pilot trials were carried out on all horses to determine the dose of NaCl (dissolved in 1,500 ml of lukewarm water and administered via a nasogastric tube) that would induce significant thirst and cause plasma protein concentration to decrease by 0.8-1.0 g/dl (representing an ~15-20% expansion of the circulating plasma volume). It was observed after NaCl administration in this manner that horses began to drink water within 20-30 min and that water intake continued intermittently up to 2.5-3 h after NaCl administration. Further water intake was not observed in any horse after 3 h had elapsed after NaCl administration. These trials revealed the NaCl dose to vary between 0.30 and 0.45 g/kg body weight for individual horses and that an interval of 4.5-5 h after NaCl administration was required to achieve the desired reduction in plasma protein concentration. Thereafter, plasma protein concentration of horses began to gradually recover toward the pre-NaCl baseline values. These observations comprised the basis for hypervolemia experiments in the present study. In the hypervolemia (hyperhydration) experiments, ~8-10 min after determination of baseline plasma protein concentration in standing horses (rest 1), a nasogastric tube was positioned and the predetermined (from pilot trials above) dose of NaCl (varying between 0.3 and 0.45 g/kg for individual horses) dissolved in 1,500 ml of lukewarm water was administered into the stomach. After NaCl administration, the horses returned to the stall where free access to fresh water was provided. Because pilot trials had revealed that water intake ceased 3 h after NaCl administration, horses were instrumented (cf. Experimental procedures) ~3.75 h after NaCl administration. After instrumentation, horses stood quietly on the treadmill. At 285-290 min after NaCl administration, plasma protein concentration and blood-gas and pH measurements were made in duplicate on quietly standing horses (hereafter, referred to as the preexercise data) when heart rate and aortic and pulmonary vascular pressures had been stable for at least 10-15 min. In the control study, horses did not receive any medications, and the plasma protein concentration and blood-gas and pH measurements were made at corresponding intervals in duplicate on quietly standing horses during steady-state conditions. The sequence of control and hypervolemia experiments was randomized for all horses, and 7 days were allowed between studies on every horse. In both treatments, after completion of preexercise measurements, exercise began on the high-speed treadmill set at a 3.5% uphill grade in the following manner. Beginning with a walk at 2 m/s for 120 s, the belt speed was raised in increments of 1 m/s every 60 s until the speed was 5 m/s. After the horses had trotted at 5 m/s for 120 s, belt speed was rapidly increased to 14 m/s. On completion of 120 s of galloping at 14 m/s on a 3.5% uphill grade, the belt speed was decreased first to 5 m/s (trot) for 60 s and then to 2 m/s. Horses walked at 2 m/s for 300 s before the treadmill was stopped. In this exercise protocol, along with continuous core temperature measurement, simultaneous arterial and mixed venous blood samples were obtained for determining blood-gas tensions, pH, hemoglobin concentration, hemoglobin O2 saturation, and O2 content at 60 and 120 s of trotting at 5 m/s; at 30, 60, 90, and 120 s of galloping at 14 m/s on a 3.5% uphill grade; and at 120 s of walk at 2 m/s. Plasma protein concentration was also determined at 120 s of trot at 5 m/s, at 120 s of galloping at 14 m/s, and at 2 min of walk at 2 m/s. Mixed venous blood lactate concentration was determined preexercise, at 120 s of trotting at 5 m/s, and on completion of the high-intensity exercise.Postexercise airway endoscopic examination. In both treatments, using a flexible fiber-optic endoscope (Pentax Fiberscopes, Orangeburg, NY), careful endoscopic examination of the nasopharynx, larynx, and trachea (up to the carina) was undertaken 45-50 min postexercise (13, 14, 28), and the presence of fresh blood in the airway(s) was regarded as indicative of the occurrence of EIPH.
Data analysis. All data were subjected to repeated-measures, split-plot design analysis of variance by using the SAS statistical software package (SAS version 8.2, SAS Institute, Cary, NC), and the treatment comparisons were made by using the least squares significant difference method (27). Data for the control as well as the hypervolemia experiments were also individually subjected to analysis of variance followed by Newman-Keuls multiple-range test (Ref. 27; SAS version 8.2, SAS Institute) to determine the significant effects of work intensity and duration within each treatment. For all statistical analyses, the level of significance was set at P < 0.05. The data are presented as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Changes in plasma protein concentration at rest and during
exercise.
Nasogastric administration of hypertonic NaCl solution was well
tolerated by the horses, and it induced marked thirst causing a total
water consumption of ~14-19 liters in individual horses within
the first 3 h after NaCl administration. Preexercise measurements revealed plasma protein concentration of standing horses to have decreased (P < 0.0001) from its baseline (pre-NaCl
administration; rest 1) value of 6.09 ± 0.11 g/dl to
5.16 ± 0.07 g/dl (Fig. 1, top), amounting to an
estimated 18.0 ± 1.8% expansion of the circulating plasma volume
(Fig. 2, top).
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Changes in hemoglobin concentration at rest and during exertion (Fig. 2, bottom). Increased plasma volume in the hyperhydration experiments also led to a marked hemodilution, causing a drop (P < 0.0001) in hemoglobin concentration of quietly standing horses. Exercise in both treatments was attended by a large rise (P < 0.0001) in the hemoglobin concentration, due probably in large measure to the release of the erythrocyte reservoir on splenic contraction. From its preexercise values of 13.6 ± 0.5 and 12.0 ± 0.6 g/dl, respectively, in the control and hypervolemia experiments, hemoglobin concentration had increased (both P < 0.0001) to reach 22.3 ± 0.3 and 19.8 ± 0.4 g/dl, respectively, at 120 s of galloping at 14 m/s on a 3.5% uphill grade. However, throughout the exercise protocol, hemoglobin concentration in the hypervolemia experiments remained less (P < 0.0001) than corresponding values in the control study.
Changes in core temperature with exercise. The extent of exercise induced hyperthermia was unaffected by hypervolemia induced after NaCl administration. From its preexercise values (37.2 ± 0.1 and 37.3 ± 0.1°C in the control and hypervolemia experiments, respectively), pulmonary artery blood temperature of horses registered progressive increments as exercise duration and intensity increased, reaching 40.7 ± 0.2 and 40.5 ± 0.2°C respectively, at 120 s of galloping at 14 m/s on a 3.5% uphill grade in the control and hypervolemia studies. At this workload, the heart rate of horses had approached its maximal value (220 ± 3 beats/min) in both treatments.
Changes in arterial O2 tension and hemoglobin
O2 saturation with exercise (Fig.
3).
Preexercise data for these variables were similar in both treatments.
During submaximal exercise performed at 5 m/s, arterial O2
tension and hemoglobin O2 saturation were not different
from preexercise values in either treatment.
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Changes in mixed venous blood O2 tension and hemoglobin O2 saturation with exercise (Fig. 3). Preexercise values of these variables were similar in the control and hypervolemia experiments. The incremental exercise protocol caused work intensity-related reductions in these variables in both treatments. Although there was a tendency for mixed venous blood O2 tension and hemoglobin O2 saturation to be lower in the hypervolemia experiments during galloping at 14 m/s on a 3.5% uphill grade, significant differences could not be demonstrated.
Changes in arterial CO2 tension with exercise (Fig. 4). Hypervolemia induced after nasogastric administration of NaCl did not affect the preexercise values of arterial CO2 tension. Whereas submaximal exercise at 5 m/s in both treatments was attended by hyperventilation, during galloping at 14 m/s on a 3.5% uphill grade marked hypercapnia (P < 0.01) developed. At 120 s of galloping at 14 m/s on a 3.5% uphill grade in the control and the hypervolemia experiments, arterial CO2 tension had reached 54.9 ± 2.4 and 51.7 ± 1.9 Torr, respectively, and significant differences between the treatments were not found. During the recovery period after high-intensity exercise, a dramatic hyperventilation ensued in both treatments.
Changes in arterial pH, and blood lactate concentration with exercise (Fig. 5). Preexercise values of arterial pH and blood lactate concentration were not different between the control and the hypervolemia experiments. In both treatments, arterial pH did not change with exercise performed at 5 m/s. During galloping at 14 m/s on a 3.5% uphill grade, a progressive acidosis of a similar magnitude was observed in both treatments. At 120 s of galloping at 14 m/s on a 3.5% uphill grade in the control and the hypervolemia experiments, the arterial pH had decreased to 7.095 ± 0.035 and 7.099 ± 0.034, respectively, as blood lactate concentration increased (P < 0.0001) to reach 19.2 ± 2.3 and 17.4 ± 1.7 mM, respectively.
Changes in arterial and mixed venous blood O2 contents
(Fig. 6).
Because of the lower hemoglobin concentration in the hypervolemia
experiments (cf. Fig. 2), preexercise values of arterial O2
content (16.3 ± 0.8 ml O2/dl blood) and mixed venous
blood O2 content (12.6 ± 0.9 ml O2/dl
blood) were also less (P < 0.01) than corresponding
values in the control study, but the arterial-to-mixed venous blood
O2 content gradient remained similar for both treatments.
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Airway endoscopic observations. All horses were observed to have experienced EIPH in both treatments as demonstrated by the presence of fresh blood in the trachea on postexercise airway endoscopic examination.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Our observations in the control study regarding significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, acidosis, hemoconcentration, increased O2 extraction, and increased blood lactate concentration (Figs. 2-6), as well as significant hyperthermia in horses performing short-term high-intensity exercise are similar to those described previously (7, 18-21). The exercise-induced changes in plasma protein concentration and contraction of plasma volume in the control experiments (Fig. 1) also mirrored data reported previously (8). Our primary objective in the present study was to examine whether significant preexercise expansion of plasma volume would accentuate the arterial hypoxemia observed in Thoroughbreds performing strenuous exercise. In this context, our data revealed that preexercise induction of significant hypervolemia in healthy horses did not significantly affect the development and/or severity of arterial hypoxemia and desaturation of hemoglobin (Fig. 3) during short-term high-intensity exercise that elicited maximal heart rate and caused stress failure of pulmonary capillaries, resulting in EIPH. These findings are in sharp contrast with those of Sosa-Leon et al. (25), wherein an expansion of plasma volume was reported to cause a mean further drop of 15 Torr in arterial O2 tension of horses performing submaximal exercise, and it was concluded that hyperhydration before exercise is detrimental to respiratory function. However, it should be noted that our observations concur with those in human subjects wherein preexercise expansion of plasma volume did not significantly affect the exercise-induced arterial hypoxemia (35). It is interesting to note that the magnitude of preexercise hypervolemia was much greater (18%) in our experiments [vs. that in the human subjects (~7.7%; Ref. 35) and in Standardbred horses (10.8% at end exercise; Ref. 25)], and yet statistically significant changes in arterial O2 tension and/or hemoglobin O2 saturation of galloping Thoroughbreds could not be demonstrated (Fig. 3).
In a comparision of the divergent results of the present study vs.
those in the hyperhydration experiments of Sosa-Leon et al.
(25), several important differences between the
experimental design and protocols of the two studies must be
recognized. First, whereas short-term maximal
exercise in Thoroughbreds was examined in the present study, in the
experiments of Sosa-Leon et al. Standardbred horses performing
submaximal exercise at 7.3-8.0 m/s (equivalent to 55-61%
O2 max) for 4 and 14 min [after
prolonged periods (lasting 30-50 min) of mild exercise at 3 m/s]
were studied. It has been reported that Thoroughbreds performing
exercise at treadmill speeds up to 8 m/s for brief periods (without
extended periods of mild exercise before such exercise), typically, do
not exhibit significant arterial hypoxemia (7,
18-21). Thus one wonders whether the prolonged periods of
mild exercise (at 3 m/s for 30-50 min) before moderate exertion at
7.3-8.0 m/s somehow contributed to the reported further
significant reduction (15 Torr) in arterial O2 tension in
their hyperhydration experiments (25). Second, whereas in the present study a significant expansion of plasma volume
was achieved preexercise (Figs. 1 and 2), this was not the case in the
experiments of Sosa-Leon et al. In that report (25), as exercise was initiated, significant changes in
plasma protein concentration and/or hematocrit had not occurred, but apparently, as a result of the continued absorption of the administered fluid from the gastrointestinal tract during the prolonged periods of
mild exercise at 3 m/s, a 10.8% expansion of plasma volume developed
at end exercise (25). Despite these differences, the fact
remains that the magnitude of preexercise hypervolemia in the present
study was greater (18.0 ± 1.8%) than that (10.8% at end
exercise) in the experiments of Sosa-Leon et al. Also, the pulmonary
capillary blood pressure of maximally exercising horses is known to far
exceed that during moderate exercise (14-17). Thus, on the basis of the mechanism proposed by Sosa-Leon et al. that pulmonary edema due to extravasation of the administered fluid may be
responsible for the further significant (15 Torr) drop in arterial
O2 tension of exercising horses in their hyperhydration experiments (25), an even larger reduction in arterial
O2 tension of maximally exercised horses would have been
expected in our hypervolemia experiments. However, this was not found
to be the case (Fig. 3). Therefore, it is believed that the above
differences in experimental design and protocols are unlikely to
account for the divergent results of the present study regarding the
lack of an effect of preexercise hypervolemia on the arterial hypoxemia in Thoroughbreds performing short-term maximal exercise.
A significant expansion of the plasma volume in our experiments was demonstrated by the significantly diminished concentrations of plasma protein and hemoglobin, both preexercise as well as during exercise (Figs. 1 and 2). Whereas the marked hemodilution did not significantly affect the arterial-to-mixed venous blood O2 content gradient in standing horses, a statistically significant (P < 0.01) attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O2 content gradient did occur (Fig. 6). Because we used the same exercise protocol for both treatments, the total (aerobic + anaerobic) energy requirement to perform the same workload in our control and hypervolemia experiments should be identical. However, after nasogastric administration of NaCl to horses, increased water intake augments body weight, which, in turn, necessitates additional ATP generation during exertion. In maximally exercising horses, the latter is probably provided by increased anaerobic metabolism, thereby causing additional lactate production. Because of greater dilution, hypervolemia (in the absence of increased body weight) would be expected to result in a lower blood lactate concentration in maximally exercising horses. However, this was not the case in the present study (Fig. 5). Thus the observed similarity of blood lactate concentration and arterial pH during maximal exercise in our hypervolemia experiments to values in the control study (Fig. 5) may be indicative of the additional lactate production necessitated by the augmented body weight.
Whole body O2 consumption is the product of cardiac output
and arterial-to-mixed venous blood O2 content gradient
(Fick principle). Thus, at constant
O2 max (during galloping at 14 m/s on a
3.5% uphill grade), the smaller arterial-to-mixed venous blood
O2 content gradient of maximally exercising horses observed in our hypervolemia experiments (Fig. 6) would have been attended by an
augmented cardiac output. This is in agreement with the observations of
Hopper et al. (11) that after preexercise acute (~20%) expansion of plasma volume, a significant (16%)
augmentation of cardiac output occurred in maximally exercising horses
(11). Because the maximal heart rate achieved during
galloping at 14 m/s on a 3.5% uphill grade was unaffected by
hypervolemia in our horses, this augmentation of cardiac output would
probably have been accomplished via increased stroke volume
(11). Similar data regarding an augmentation of cardiac
output and stroke volume have also been reported in human subjects
performing strenuous exercise after acute hypervolemia (12,
31). It has been reported that the high packed cell volume
(hematocrit approaching 65-68% in our control study) in galloping
Thoroughbreds contributes to the observed high values of blood
viscosity (6), which pose an impediment to blood
flow. Thus hemodilution by way of lowering blood viscosity
[and, therefore, resistance to blood flow (i.e., ventricular
afterload)] in our hypervolemia experiments may have contributed to an
augmentation of stroke volume in galloping horses. Other factors
contributing to an augmentation of stroke volume may include enhanced
ventricular filling (via Frank-Starling mechanism) and augmented
cardiac contractility (11, 12, 31).
The above discussion regarding an augmentation of cardiac output in hypervolemic horses performing maximal exertion (11) is quite relevant to the mechanism(s) for exercise-induced arterial hypoxemia (Fig. 3). Although relative hypoventilation [as demonstrated by increased arterial CO2 tension (Fig. 4) despite increased alveolar ventilation in galloping horses] and ventilation-perfusion inhomogeneity also contribute (1, 5, 29, 30), the largest contribution to exercise-induced arterial hypoxemia in racehorses is from diffusion limitation to transfer of O2 (30). The latter is probably related to the significant shortening of the transit time for blood in the pulmonary capillaries as cardiac output increases dramatically (5). The scenario that galloping horses in our hypervolemia experiments may have had augmented cardiac output (11), in turn, suggests that there would have been a further truncation of the already shortened pulmonary capillary transit time during high-intensity exercise, which should have adversely affected the arterial O2 tension. However, this was not found to be the case in the present study (Fig. 3), presumably because hypervolemia may also have affected pulmonary capillary blood volume and the distribution of ventilation-perfusion mismatching within the lungs, thereby affecting pulmonary gas exchange of exercising horses. Although in a recent report (35) acute hypervolemia also failed to significantly affect the exercise-induced arterial hypoxemia in human subjects, it should be noted that acute hypervolemia in that study was reported to cause a significant increase in the pulmonary transit time despite the lack of a significant change in cardiac output (35). However, it remained unclear as to what fraction of the measured pulmonary transit time (35) represented the "true" pulmonary capillary transit time and whether the latter and/or pulmonary capillary blood volume were affected by acute hypervolemia. The extent of exercise-induced arterial hypercapnia in our experiments was not significantly affected by preexercise induction of hypervolemia (Fig. 4), indicating similarity of alveolar ventilation in the two treatments.
In agreement with previous findings (7, 18-21), in the present study arterial hypoxemia was also found to be well developed at 30 s of galloping at 14 m/s on a 3.5% uphill grade in both treatments, and its severity did not change with increasing exercise duration (Fig. 3). Recently, Préfaut et al. (22, 23) suggested that pulmonary capillary stress failure-induced airway inflammatory mediator release plays a role in bringing about the exercise-induced arterial hypoxemia. That all horses in the present study had experienced pulmonary capillary stress failure, was demonstrated by the occurrence of EIPH in both treatments. According to the pulmonary injury-evoked airway inflammatory mediator release hypothesis (22, 23), an accentuation of arterial hypoxemia would be expected to occur with increasing exercise duration as structural changes in the blood-gas barrier (2, 24, 32) intensify over time. Although this hypothesis has considerable appeal, the findings of Wetter et al. (33, 34) in exercising young human subjects did not lend credence to it. Similarly, our laboratory's recent work with pretreatment of Thoroughbreds with dexamethasone (to suppress the airway inflammatory response) and with a potent antihistaminic agent (tripelennamine HCl, an H1-receptor antagonist) to mitigate the effects of airway inflammatory- and mast cell-released histamine on pulmonary capillary permeability also did not support the pulmonary injury hypothesis for exercise-induced arterial hypoxemia in racehorses (20, 21).
In summary, our data revealed that preexercise 18% expansion of plasma volume failed to significantly affect the development and/or severity of arterial hypoxemia in Thoroughbred horses performing short-term high-intensity exercise that elicited maximal heart rate and caused stress failure of pulmonary capillaries resulting in EIPH. Furthermore, it was observed that blood lactate concentration and arterial pH of maximally exercising horses were unaffected by preexercise hypervolemia. Although hemodilution caused a significant attenuation of the exercise-induced expansion of the arterial to mixed venous blood O2 content gradient in our horses, it likely was offset by an augmented cardiac output.
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ACKNOWLEDGEMENTS |
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The authors gratefully acknowledge the excellent technical assistance provided by Sarah Humphrey, Tracy DePuy, William Love, Jason Bundy, Walter C. Crackel, and Beth Saupe.
This work was supported in part by grants-in-aid from the Houston Equine Research Organization, the US Department of Agriculture-Hatch funds, the Illinois Department of Agriculture Equine Research Fund, and the Illinois Thoroughbred Horsemen's Association. The high-speed treadmill at the University of Illinois College of Veterinary Medicine was procured in part with financial support provided by the Illinois Thoroughbred and Standardbred Breeder's Fund.
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FOOTNOTES |
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Address for reprint requests and other correspondence: M. Manohar, University of Illinois, College of Veterinary Medicine, 212 Large Animal Clinic, 1102 W. Hazelwood Dr., Urbana, IL 61802 (E-mail: mmanohar{at}uiuc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published January 31, 2003;10.1152/japplphysiol.00973.2002
Received 22 October 2002; accepted in final form 29 January 2003.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Bayly, WM,
Hodgson DR,
Schultz DA,
Dempsey JA,
and
Gollnick PD.
Exercise-induced hypercapnia in the horse.
J Appl Physiol
67:
1858-1866,
1989.
2.
Birks, EK,
Mathieu-Costello O,
Zhenxing F,
Tyler WS,
and
West JB.
Very high pressures are required to cause stress failure of pulmonary capillaries in Thoroughbred racehorses.
J Appl Physiol
82:
1584-1592,
1997.
3.
Boyd, JW.
The relationships between blood hemoglobin concentration, packed cell volume, and plasma protein concentration in dehydration.
Br Vet J
137:
166-172,
1981.
4.
Caillaud, CF,
Anselme FM,
and
Préfaut CG.
Effects of two successive maximal exercise tests on pulmonary gas exchange.
Eur J Appl Physiol
74:
141-147,
1996.
5.
Dempsey, JA,
and
Wagner PD.
Exercise-induced arterial hypoxemia.
J Appl Physiol
87:
1997-2006,
1999.
6.
Fedde, MR,
Ho HH,
and
Wood SC.
Oxygen transport in exercising horses: importance of rheological properties of blood.
In: The Vertebrate Gas Transport Cascade-Adaptations to Environment and Mode of Life, edited by Bicudo JEPW. London: CRC, 1993, p. 200-207.
7.
Goetz, TE,
Manohar M,
Hassan AS,
and
Baker GJ.
Nasal strips do not affect pulmonary gas-exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds.
J Appl Physiol
90:
2378-2385,
2001.
8.
Goetz, TE,
Manohar M,
and
Magid JH.
Repeated administration of furosemide does not offer an advantage over single dosing in attenuating exercise-induced pulmonary hypertension in Thoroughbred horses.
Equine Vet J Suppl
30:
539-545,
1999.
9.
Hanel, B,
Clifford P,
and
Secher N.
Restricted postexercise pulmonary diffusion capacity does not impair maximal transport of O2.
J Appl Physiol
77:
2408-2412,
1994.
10.
Hopkins, SR,
Schoene RB,
Martin TR,
Henderson WR,
Spragg RG,
and
West JB.
Intense exercise impairs the integrity of the pulmonary blood-gas barrier in elite athletes.
Am J Respir Crit Care Med
155:
1090-1094,
1997.
11.
Hopper, MK,
Pieschl RL,
Pelletier JG,
and
Erickson HH.
Cardiopulmonary effects of acute blood volume alteration prior to exercise.
In: Equine Exercise Physiology 3, edited by Persson SGB,
Lindholm A,
and Jeffcoat LB.. Davis, CA: ICEEP Publications, 1991, p. 9-16.
12.
Kanstrup, IL,
and
Eckblom B.
Acute hypervolemia, cardiac performance, and aerobic power during exercise.
J Appl Physiol
52:
1186-1191,
1982.
13.
LaPointe, JM,
Vrins A,
and
McCarvill E.
A survey of exercise-induced pulmonary hemorrhage in Quebec Standardbred racehorses.
Equine Vet J
26:
482-485,
1994.
14.
Manohar, M,
and
Goetz TE.
Pulmonary vascular pressures of exercising Thoroughbred horses with and without endoscopic evidence of EIPH.
J Appl Physiol
81:
1589-1593,
1996.
15.
Manohar, M,
and
Goetz TE.
L-NAME does not affect exercise-induced pulmonary hypertension in Thoroughbred horses.
J Appl Physiol
84:
1902-1908,
1998.
16.
Manohar, M,
and
Goetz TE.
Pulmonary vascular pressures of strenuously exercising Thoroughbreds during intravenous infusion of nitroglycerin.
Am J Vet Res
60:
1436-1440,
1999.
17.
Manohar, M,
and
Goetz TE.
Pulmonary vascular resistance of horses decreases with moderate exercise and remains constant as workload is increased to maximal exercise.
Equine Vet J Suppl
30:
117-121,
1999.
18.
Manohar, M,
Goetz TE,
and
Hassan AS.
Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses.
J Appl Physiol
90:
2371-2377,
2001.
19.
Manohar, M,
Goetz TE,
and
Hassan AS.
Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses.
J Appl Physiol
91:
1105-1112,
2001.
20.
Manohar, M,
Goetz TE,
Humphrey S,
and
DePuy T.
H1-receptor antagonist, tripelennamine, does not affect arterial hypoxemia in exercising Thoroughbreds.
J Appl Physiol
92:
1515-1523,
2002.
21.
Manohar, M,
Goetz TE,
Hassan AS,
DePuy T,
and
Humphrey S.
Anti-inflammatory agent, dexamethasone, does not affect exercise-induced arterial hypoxemia in Thoroughbreds.
J Appl Physiol
93:
99-106,
2002.
22.
Préfaut, C,
Anselme PF,
and
Caillaud C.
Inhibition of histamine release by nedocromil sodium reduces exercise-induced hypoxemia in master athletes.
Med Sci Sports Exerc
29:
10-16,
1997.
23.
Préfaut, C,
Durand F,
Mucci P,
and
Caillaud C.
Exercise-induced arterial hypoxemia in athletes.
Sports Med
30:
47-61,
2000.
24.
Schaffartzik, W,
Arcos J,
Tsukimoto AK,
Mathieu-Costello O,
and
Wagner PD.
Pulmonary interstitial edema in the pig after heavy exercise.
J Appl Physiol
75:
2535-2540,
1993.
25.
Sosa-Leon, L,
Hodgson DR,
Evans DL,
Ray SP,
Carlson GP,
and
Rose RJ.
Hyperhydration prior to moderate-intensity exercise causes arterial hypoxemia.
Equine Vet J Suppl
34:
425-429,
2002.
26.
St. Croix, CM,
Harms CA,
McClaran SR,
Nickele GA,
Pegelow DF,
Nelson WB,
and
Dempsey JA.
Effects of prior exercise on exercise-induced arterial hypoxemia in young women.
J Appl Physiol
85:
1556-1563,
1998.
27.
Steel, RGD,
and
Torrie JH.
Principles and Procedures in Statistics (2nd ed.). New York: McGraw-Hill, 1960, p. 138-206.
28.
Sweeney, CR.
Exercise-induced pulmonary hemorrhage.
Vet Clin North Am Equine Pract
7:
93-104,
1991.
29.
Wagner, PD,
Erickson BK,
Seaman J,
Kubo A,
Hiraga M,
Kai M,
and
Yamaya Y.
Effects of altered FIO2 on maximal O2 in the horse.
Respir Physiol
105:
123-134,
1996.
30.
Wagner, PD,
Gillespie JR,
Landgren GL,
Fedde MR,
Jones BW,
DeBowes RM,
Pieschl RL,
and
Erickson HH.
Mechanism of exercise-induced hypoxemia in horses.
J Appl Physiol
66:
1227-1233,
1989.
31.
Warburton, DE,
Gledhill N,
Jamnik VK,
Krip B,
and
Card N.
Induced hypervolemia, cardiac function, O2 max, and performance of elite cyclists.
Med Sci Sports Exerc
31:
800-808,
1999.
32.
West, JB,
Mathieu-Costello O,
Jones JH,
Birks EK,
Logeman RB,
Pascoe JR,
and
Tyler WS.
Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage.
J Appl Physiol
75:
1097-1109,
1993.
33.
Wetter, TJ,
St. Croix C,
Pegelow DF,
Sonetti DA,
and
Dempsey JA.
Effects of exhaustive endurance exercise on pulmonary gas exchange and airway function in women.
J Appl Physiol
91:
847-858,
2001.
34.
Wetter, TJ,
Xiang Z,
Sonetti DA,
Haverkamp HC,
Rice AJ,
Abbasi AA,
Meyer KC,
and
Dempsey JA.
Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.
J Appl Physiol
93:
116-126,
2002.
35.
Zavorsky, GS,
Walley KR,
Hunte GS,
McKenzie DC,
Sexsmith GP,
and
Russell JA.
Acute hypervolemia lengthens red cell pulmonary transit time during exercise in endurance athletes.
Respir Physiolo Neurobiol
131:
255-268,
2002.
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Statistically significant difference from
corresponding data for rest 1 in the same study,
P < 0.0001. 
Statistically
significant difference from preexercise value in standing horses in the
same study, P < 0.0001. 
Statistically significant difference from values at
5 m/s in the same study, P < 0.0001. 
Statistically significant difference from
corresponding data in the control study, P < 0.0001.
Statistically significant difference from
data at 30 s of galloping at 14 m/s on a 3.5% uphill grade in the
same study, P < 0.05. 
Statistically
significant difference from preexercise as well as all exercise data,
P < 0.0001.
Statistically significant difference from 90 s
of galloping at 14 m/s on a 3.5% uphill grade in the same study,
P < 0.05.
Statistically
significant difference from all data for exercise at 5 as well as 14 m/s on a 3.5% uphill grade, P < 0.0001.