Preexercise hypervolemia does not affect arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise.

It is reported that preexercise hyperhydration caused arterial O(2) 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 H(2)O) 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 O(2) content gradient.     

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.     

NaHCO(3) does not affect arterial O(2) tension but attenuates desaturation of hemoglobin in maximally exercising Thoroughbreds.

The objective of the present study was to examine the effects of preexercise NaHCO(3) administration to induce metabolic alkalosis on the arterial oxygenation in racehorses performing maximal exercise. Two sets of experiments, intravenous physiological saline and NaHCO(3) (250 mg/kg i.v.), were carried out on 13 healthy, sound Thoroughbred horses in random order, 7 days apart. Blood-gas variables were examined at rest and during incremental exercise, leading to 120 s of galloping at 14 m/s on a 3.5% uphill grade, which elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. NaHCO(3) administration caused alkalosis and hemodilution in standing horses, but arterial O(2) tension and hemoglobin-O(2) saturation were unaffected. Thus NaHCO(3) administration caused a reduction in arterial O(2) content at rest, although the arterial-to-mixed venous blood O(2) content gradient was unaffected. During maximal exercise in both treatments, arterial hypoxemia, desaturation, hypercapnia, acidosis, hyperthermia, and hemoconcentration developed. Although the extent of exercise-induced arterial hypoxemia was similar, there was an attenuation of the desaturation of arterial hemoglobin in the NaHCO(3)-treated horses, which had higher arterial pH. Despite these observations, the arterial blood O(2) content of exercising horses was less in the NaHCO(3) experiments because of the hemodilution, and an attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O(2) content gradient was observed. It was concluded that preexercise NaHCO(3) administration does not affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing short-term, high-intensity exercise.     

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.     

H1-receptor antagonist, tripelennamine, does not affect arterial hypoxemia in exercising Thoroughbreds.

It has been suggested that pulmonary injury and inflammation-induced histamine release from airway mast cells may contribute to exercise-induced arterial hypoxemia (EIAH). Because stress failure of pulmonary capillaries and EIAH are routinely observed in exercising horses, we examined whether preexercise administration of an H1-receptor antagonist may mitigate EIAH. Two sets of experiments, placebo (saline) and antihistaminic (tripelennamine HCl at 1.10 mg/kg iv, 15 min preexercise) studies, were carried out on seven healthy, exercise-trained Thoroughbred horses in random order 7 days apart. Arterial and mixed venous blood-gas and pH measurements were made at rest before and after saline or drug administration and during incremental exercise leading to maximal exertion at 14 m/s on 3.5% uphill grade for 120 s. Galloping at this workload elicited maximal heart rate and induced exercise-induced pulmonary hemorrhage in all horses in both treatments, thereby indicating that capillary stress failure-related pulmonary injury had occurred. In both treatments, EIAH, desaturation of hemoglobin, hypercapnia, and acidosis of a similar magnitude developed during maximal exertion, and statistically significant differences between the placebo and antihistaminic studies could not be demonstrated. The failure of the H1-receptor antagonist to modify EIAH significantly suggests that pulmonary injury-induced histamine release may not play a major role in bringing about EIAH in Thoroughbred horses.     

NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses.

In horses, the exercise-induced elevation of pulmonary arterial pressure (Ppa) is thought to play a deterministic role in exercise-induced pulmonary hemorrhage (EIPH), and thus treatment designed to lower Ppa might reasonably be expected to reduce EIPH. Five Thoroughbred horses were run on a treadmill to volitional fatigue (incremental step test) under nitric oxide (NO; inhaled 80 ppm) and control (N(2), same flow rate as per NO run) conditions (2 wk between trials; order randomized) to test the hypothesis that NO inhalation would reduce maximal Ppa but that this reduction may not necessarily reduce EIPH. Before each investigation, a microtipped pressure transducer was placed in the pulmonary artery 8 cm past the pulmonic valve to monitor Ppa. EIPH severity was assessed via bronchoalveolar lavage (BAL) 30 min postrun. Exercise time did not differ between the two trials (P > 0.05). NO administration resulted in a small but consistent and significant reduction in peak Ppa (N(2), 102.3 +/- 4.4; NO, 98.6 +/- 4.3 mmHg, P < 0.05). In the face of lowered Ppa, EIPH severity was significantly higher in the NO trial (N(2), 22.4 +/- 6.8; NO, 42.6 +/- 15.4 x 10(6) red blood cells/ml BAL fluid, P < 0.05). These findings support the notion that extremely high Ppa may reflect, in part, an arteriolar vasoconstriction that serves to protect the capillary bed from the extraordinarily high Ppa evoked during maximal exercise in the Thoroughbred horse. Furthermore, these data suggest that exogenous NO treatment during exercise in horses may not only be poor prophylaxis but may actually exacerbate the severity of EIPH.     

Metabolic consequences of reduced frequency breathing during submaximal exercise at moderate altitude

The intention of this study was to determine the metabolic consequences of reduced frequency breathing (RFB) at total lung capacity (TLC) in competitive cyclists during submaximal exercise at moderate altitude (1520 m; barometric pressure, PB = 84.6 kPa; 635 mm Hg). Nine trained males performed an RFB exercise test (10 breaths.min-1) and a normal breathing exercise test at 75-85% of the ventilatory threshold intensity for 6 min on separate days. RFB exercise induced significant (P less than 0.05) decreases in ventilation (VE), carbon dioxide production (VCO2), respiratory exchange ratio (RER), ventilatory equivalent for O2 consumption (VE/VO2), arterial O2 saturation and increases in heart rate and venous lactate concentration, while maintaining a similar O2 consumption (VO2). During recovery from RFB exercise (spontaneous breathing) a significant (P less than 0.05) decreases in blood pH was detected along with increases in VE, VO2, VCO2, RER, and venous partial pressure of carbon dioxide. The results indicate that voluntary hypoventilation at TLC, during submaximal cycling exercise at moderate altitude, elicits systemic hypercapnia, arterial hypoxemia, tissue hypoxia and acidosis. These data suggest that RFB exercise at moderate altitude causes an increase in energy production from glycolytic pathways above that which occurs with normal breathing.     

Anti-inflammatory agent, dexamethasone, does not affect exercise-induced arterial hypoxemia in Thoroughbreds.

In view of the suggestion that pulmonary injury-induced release of histamine and/or other chemical mediators from airway inflammatory and mast cells contribute to the exercise-induced arterial hypoxemia (EIAH) in human athletes, we examined the effects of pretreatment with a potent anti-inflammatory agent, dexamethasone, on EIAH and desaturation of hemoglobin in horses. Seven healthy, sound, exercise-trained Thoroughbreds were studied in the control (no medications) experiments, followed in 7 days by intravenous dexamethasone (0.11 mg.kg(-1).day(-1) for 3 consecutive days) studies. Blood-gas measurements were made at rest and during incremental exercise leading to maximal exertion at 14 m/s on a 3.5% uphill grade. Galloping at this workload induced pulmonary hemorrhage in all horses in both treatments, thereby indicating that stress failure of pulmonary capillaries had occurred. In both treatments, significant EIAH, desaturation of hemoglobin, hypercapnia, acidosis, and hyperthermia developed during maximal exercise, but significant differences between the control and dexamethasone treatments were not discerned. The failure of pretreatment with dexamethasone to significantly affect EIAH suggests that pulmonary injury-evoked airway inflammatory response may not play a major role in EIAH in racehorses. However, our observations in both treatments that EIAH developed quickly (being evident at 30 s of exertion) and that its severity remained unaffected by increasing exercise duration (to 120 s) suggest that EIAH has a functional basis, probably related to significant shortening of the transit time for blood in the pulmonary capillaries as cardiac output increases dramatically.     

Effect of breathing of a helium-oxygen mixture on adaptation to effort in humans during high-altitude hypoxia

The study was carried out on 17 healthy males aged 20-27 years subjected for 15 minutes to submaximal effort on a cycle ergometer (Elema-Schonander) under conditions of breathing ambient atmospheric air or a helium-oxygen mixture (20% O2 + 80% He) and under hypobaric pressure simulating an altitude of 3500 m above sea level. During the experiment the heart rate was recorded with ECG, and determinations were performed of the minute volume, respiratory rate, tidal volume and systolic arterial blood pressure. In the serum of venous blood obtained before and 3 minutes after the exercise the concentrations were measured of lactate (LA), pyruvate (PA) and glucose. High-altitude hypoxia caused unifavourable changes in the adaptation to effort manifesting themselves as an increase of the values of the determined physiological and biochemical indices. On the other hand, favourable changes were observed of the reaction to exercise while the subjects were breathing the helium-oxygen mixture during high-altitude hypoxia. The minute volume increased owing to increased tidal volume, and the exercise-induced rise of lactate (LA), pyruvate (PA) and the LA/PA ratio was lower. This may suggest reduced energy cost of respiration and reduced anaerobic metabolism under these conditions.     

Efficacy of nasal strip and furosemide in mitigating EIPH in Thoroughbred horses.

The purpose of this investigation was to study the effects of an equine nasal strip (NS), furosemide (Fur), and a combination of both (NS + Fur) on exercise-induced pulmonary hemorrhage (EIPH) at speeds corresponding to near-maximal effort. Five Thoroughbreds (526 +/- 25 kg) were run on a flat treadmill from 7 to 14 m/s in 1 m x s(-1) x min(-)1 increments every 2 wk (treatment order randomized) under control (Con), Fur (1 mg/kg iv 4 h prior), NS, or NS + Fur conditions. During each run, pulmonary arterial (Ppa) and esophageal (Pes) pressures were measured. Severity of EIPH was quantified via bronchoalveolar lavage (BAL) 30 min postrun. Furosemide (Fur and NS + Fur trials) reduced peak Ppa approximately 7 mmHg compared with Con (P < 0.05) whereas NS had no effect (P > 0.05). Maximal Pes swings were not different among groups (P > 0.05). NS significantly diminished EIPH compared with the Con trial [Con, 55.0 +/- 36.2; NS, 30.8 +/- 21.8 x 10(6) red blood cells (RBC)/ml BAL fluid; P < 0.05]. Fur reduced EIPH to a greater extent than NS (5.2 +/- 3.0 x 10(6) RBC/ml BAL; P < 0.05 vs. Con and NS) with no additional benefit from NS + Fur (8.5 +/- 4.2 x 10(6) RBC/ml BAL; P > 0.05 vs. Fur, P < 0.05 vs. Con and NS). In conclusion, although both modalities (NS and Fur) were successful in mitigating EIPH, neither abolished EIPH fully as evaluated via BAL. Fur was more effective than NS in constraining the severity of EIPH. The simultaneous use of both interventions appears to offer no further gain with respect to reducing EIPH.     

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 +/- 0.20 l/min at sea level to 1.17 +/- 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 +/- 1 Torr and PCO2 = 11 +/- 1 Torr, with a marked reduction in mixed venous PO2 [14.8 +/- 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.     

Pulmonary vascular pressures of exercising Thoroughbred horses with and without endoscopic evidence of EIPH

Manohar, Murli, and Thomas E. Goetz. Pulmonary vascularpressures of exercising Thoroughbred horses with and without endoscopicevidence of EIPH. J. Appl. Physiol.81(4): 1589-1593, 1996.Exercise-induced pulmonary hemorrhage(EIPH) is a common occurrence in racehorses. The objective of thisstudy was to compare pulmonary vascular pressures of healthyThoroughbred horses with and without postexertion endoscopicallydetectable fresh blood in the trachea. The nasopharynx, larynx, andtrachea (down to the carina) of horses were examined weekly with anendoscope 55-60 min postexertion, and the diagnosis of EIPH wasconfirmed by the presence of fresh blood in the trachea. Measurementsof heart rate and right atrial, pulmonary arterial, and pulmonaryarterial wedge pressures were made during quiet rest and duringtreadmill exercise performed at 14.5 m/s on a 5% uphillgrade. This workload elicited maximal heart rate of thehorses. Mean pulmonary capillary pressure was estimated to be halfwaybetween the mean pulmonary arterial pressure and the mean pulmonaryarterial wedge pressure. These data from 7 healthy soundexercise-trained horses that were positive on 12 consecutive occasions(at 1-wk intervals) for the postexercise presence of fresh blood in thetrachea were compared with those in 8 healthy horses that wereconsistently negative for the evidence of fresh blood in the trachea onpostexercise endoscopic examination over 12-16 wk. The heart rateand the right heart and/or pulmonary vascular pressures in the twogroups of horses were similar at rest. Exercise wasattended by a large significant (P < 0.05) increase in these pressures and heart rate in both groups.However, statistically significant differences between endoscopicallyEIPH-positive and endoscopically EIPH-negative horses for heart rateand right atrial and pulmonary vascular pressures were not found duringexercise. Thus these data revealed that the magnitude ofexercise-induced right atrial as well as pulmonary arterial, capillary,and venous hypertension in endoscopically EIPH-positive horses that areotherwise healthy is quite similar to that in endoscopicallyEIPH-negative horses during comparable exertion.

     

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.     

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cyclo-ergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH (P < 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 +/- 87.8 vs. 1,035.9 +/- 114.8 nmol.ml(-1).min(-1); P < 0.05) and 41 mM (2,562.0 +/- 145.0 vs. 1,618.1 +/- 149.4 nmol.ml(-1).min(-1); P < 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM (P < 0.05) and 41 mM (P < 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM (r = -0.82, P < 0.05) and 41 mM (r = -0.84, P < 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity.     

Lactate concentration differences in plasma, whole blood, capillary finger blood and erythrocytes during submaximal graded exercise in humans

The aim of the study was to investigate the distribution of lactate in plasma, whole blood, erythrocytes, and capillary finger blood, before and during submaximal exercise. Ten healthy male subjects performed submaximal graded cycle ergometer exercise for 20-25 min. Venous blood samples and capillary finger blood samples were taken before exercise and every 5th min during exercise for lactate determination. The plasma lactate concentration was significantly higher (P less than 0.001, approximately 50%) than in the erythrocytes. This difference was not altered by the venous blood lactate concentration or exercise intensity. A significant difference (P less than 0.01) in lactate concentration was also found between capillary whole blood and venous whole blood. It was concluded that direct comparisons between lactate in capillary finger blood, venous whole blood and plasma could not be made.     

Exercise hyperventilation in patients with McArdle's disease

This study was undertaken to determine if patients who lack muscle phosphorylase (i.e., McArdle's disease), and therefore the ability to produce lactic acid during exercise, demonstrate a normal hyperventilatory response during progressive incremental exercise. As expected these patients did not increase their blood lactate above resting levels, whereas the blood lactate levels of normal subjects increased 8- to 10-fold during maximal exercise. The venous pH of the normal subjects decreased markedly during exercise that resulted in hyperventilation. The patients demonstrated a distinct increase in ventilation with respect to O2 consumption similar to that seen in normal individuals during submaximal exercise. However their hyperventilation resulted in an increase in pH because there was no underlying metabolic acidosis. End-tidal partial pressures of O2 and CO2 also reflected a distinct hyperventilation in both groups at approximately 70-85% maximal O2 consumption. These data show that hyperventilation occurs during intense exercise, even when there is no increase in plasma [H+]. Since arterial CO2 levels were decreasing and O2 levels were increasing during the hyperventilation, it is possible that nonhumoral stimuli originating in the active muscles or in the brain elicit the hyperventilation observed during intense exercise.     

Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake

Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide-treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity.     

Cerebrospinal fluid acid-base balance during muscular exercise

Ventilation, metabolism, arterial blood gases, and blood and cerebrospinal fluid (CSF) acid-base status were measured in exercise studies on seven ponies during mild, moderate, and near-maximal treadmill exercise. CSF and arterial blood were sampled via indwelling catheters. Generally measurements were made during the 3rd, 6th, and 9th minute of steady-state exercise, with CSF sampled only during the 9th minute. Alveolar ventilation (VA) and metabolic rate (VO2) increased proportionately during exercise below the anaerobic threshold, but above this threshold, VA increased at a faster rate than VO2. The similarity of these response to those observed in man suggests the pony is a suitable animal model for study of exercise hyperpnea. No change in CSF acid-base balance occurred with light-to-moderate work; however, with near-maximal work a fall in CSF carbon dioxide partial pressure due to hyperventilation caused CSF to become alkaline (pH = 7.380) relative to rest (pH = 7.330). CSF lactate increased slightly with exercise but had no effect on CSF [HCO3-], which remained constant from rest to severe exercise. We conclude that it is unlikely the hyperpnea at any intensity of exercise results from an increased H+ stimulation at the medullary chemoreceptor.     

Dynamic exercise training in foxhounds. I. Oxygen consumption and hemodynamic responses

Ten foxhounds were studied during maximal and submaximal exercise on a motor-driven treadmill before and after 8-12 wk of training. Training consisted of working at 80% of maximal heart rate 1 h/day, 5 days/wk. Maximal O2 consumption (VO2max) increased 28% from 113.7 +/- 5.5 to 146.1 +/- 5.4 ml O2 X min-1 X kg-1, pre- to posttraining. This increase in VO2max was due primarily to a 27% increase in maximal cardiac output, since maximal arteriovenous O2 difference increased only 4% above pretraining values. Mean arterial pressure during maximal exercise did not change from pre- to posttraining, with the result that calculated systemic vascular resistance (SVR) decreased 20%. There were no training-induced changes in O2 consumption, cardiac output, arteriovenous O2 difference, mean arterial pressure, or SVR at any level of submaximal exercise. However, if post- and pretraining values are compared, heart rate was lower and stroke volume was greater at any level of submaximal exercise. Venous lactate concentrations during a given level of submaximal exercise were significantly lower during posttraining compared with pretraining, but venous lactate concentrations during maximal exercise did not change as a result of exercise training. These results indicate that a program of endurance training will produce a significant increase in VO2max in the foxhound. This increase in VO2max is similar to that reported previously for humans and rats but is derived primarily from central (stroke volume) changes rather than a combination of central and peripheral (O2 extraction) changes.     

Regulation of lactic acid production during exercise

Lactic acid accumulates in contracting muscle and blood beginning at approximately 50-70% of the maximal O2 uptake, well before the aerobic capacity is fully utilized. The classical explanation has been that part of the muscle is O2 deficient and therefore lactate production is increased to provide supplementary anaerobically derived energy. Currently, however, the predominant view is that lactate production during submaximal dynamic exercise is not O2 dependent. In the present review, data and arguments in support of and against the hypothesis of O2 dependency have been scrutinized. Data underlying the conclusion that lactate production during exercise is not O2 dependent were found to be 1) questionable, or 2) interpretable in an alternative manner. Experiments in human and animal muscles under various conditions demonstrated that the redox state of the muscle is reduced (i.e., NADH is increased) either before or in parallel with increases in muscle lactate. Based on experimental data and theoretical considerations, it is concluded that lactate production during submaximal exercise is O2 dependent. The amount of energy provided through the anaerobic processes during steady-state submaximal exercise is, however, low, and the role of lactate formation as an energy source is of minor importance. It is proposed that the achievement of increased aerobic energy formation under conditions of limiting O2 availability requires increases of ADP, Pi, and NADH and that the increases in ADP (and therefore AMP via the adenylate kinase equilibrium) and Pi will stimulate glycolysis, and the resulting increase in cytosolic NADH will shift the lactate dehydrogenase equilibrium toward increased lactate production.