The Physiological and Biochemical Response of Standardbred Horses to Exercise of Varying Speed and Duration

LINDHOLM, ARNE and BENGT SALTIN: The physiological and biochemical response of standardbred horses to exercise of varying speed and duration. Acta vet. scand. 1974, 15, 310–324. — Welltrained standardbred horses were studied to examine the metabolic response to excercise of various speeds and duration. Comparisons between interval (400, 700, 1,000 and 2,000 m) and continuous trotting (1 hr., 2 hrs.) and racing were made. Muscle and rectal temperatures were recorded before and immediately after each work bout. Heart rate was linearly related to trotting speed, and maximal heart rate (240 beats × min.−1) was achieved when trotting at least 700 m at close to maximal speed (12.0–12.5 m×sec.−1). Biopsy specimens from the gluteus medius muscle and venous blood were obtained before and after each work bout. Muscle and blood lactate values were markedly increased first at speeds close to maximal speed (11.4–12.5 m×sec.−1). Trotting 6×700 m at 12.5 m×sec.−1 produced as high muscle and blood lactate values as 23.7 and 19.0 mmol×kg−1 wet weight and l−1, respectively. Corresponding values after a race were about 15 mmol×kg−1 (muscle) and l−1 (blood). Glycogen utilization was related to work intensity and was most pronounced during the first work bouts. At a speed of 12 m×sec.−1 and trotting 2000 m, there was a glycogen utilization of near 12 mmol glucose units × kg−1 × min.−1 wet muscle. It is concluded that interval training over a distance of 700–1000 m repeated 4–6 times with a trotting speed close to maximal speed (11.4–12.5 m×sec.−1) appears to be optimal. ATP; CP; blood lactate; glycogen utilization; heart rate; horse skeletal muscle; muscle lactate; racing training.     

Determinants of metabolic cost during submaximal cycling.

The metabolic cost of producing submaximal cycling power has been reported to vary with pedaling rate. Pedaling rate, however, governs two physiological phenomena known to influence metabolic cost and efficiency: muscle shortening velocity and the frequency of muscle activation and relaxation. The purpose of this investigation was to determine the relative influence of those two phenomena on metabolic cost during submaximal cycling. Nine trained male cyclists performed submaximal cycling at power outputs intended to elicit 30, 60, and 90% of their individual lactate threshold at four pedaling rates (40, 60, 80, 100 rpm) with three different crank lengths (145, 170, and 195 mm). The combination of four pedaling rates and three crank lengths produced 12 pedal speeds ranging from 0.61 to 2.04 m/s. Metabolic cost was determined by indirect calorimetery, and power output and pedaling rate were recorded. A stepwise multiple linear regression procedure selected mechanical power output, pedal speed, and pedal speed squared as the main determinants of metabolic cost (R(2) = 0.99 +/- 0.01). Neither pedaling rate nor crank length significantly contributed to the regression model. The cost of unloaded cycling and delta efficiency were 150 metabolic watts and 24.7%, respectively, when data from all crank lengths and pedal speeds were included in a regression. Those values increased with increasing pedal speed and ranged from a low of 73 +/- 7 metabolic watts and 22.1 +/- 0.3% (145-mm cranks, 40 rpm) to a high of 297 +/- 23 metabolic watts and 26.6 +/- 0.7% (195-mm cranks, 100 rpm). These results suggest that mechanical power output and pedal speed, a marker for muscle shortening velocity, are the main determinants of metabolic cost during submaximal cycling, whereas pedaling rate (i.e., activation-relaxation rate) does not significantly contribute to metabolic cost.     

Effects of obesity and sex on the energetic cost and preferred speed of walking.

The metabolic energy cost of walking is determined, to a large degree, by body mass, but it is not clear how body composition and mass distribution influence this cost. We tested the hypothesis that walking would be most expensive for obese women compared with obese men and normal-weight women and men. Furthermore, we hypothesized that for all groups, preferred walking speed would correspond to the speed that minimized the gross energy cost per distance. We measured body composition, maximal oxygen consumption, and preferred walking speed of 39 (19 class II obese, 20 normal weight) women and men. We also measured oxygen consumption and carbon dioxide production while the subjects walked on a level treadmill at six speeds (0.50-1.75 m/s). Both obesity and sex affected the net metabolic rate (W/kg) of walking. Net metabolic rates of obese subjects were only approximately 10% greater (per kg) than for normal-weight subjects, and net metabolic rates for women were approximately 10% greater than for men. The increase in net metabolic rate at faster walking speeds was greatest in obese women compared with the other groups. Preferred walking speed was not different across groups (1.42 m/s) and was near the speed that minimized gross energy cost per distance. Surprisingly, mass distribution (thigh mass/body mass) was not related to net metabolic rate, but body composition (% fat) was (r2= 0.43). Detailed biomechanical studies of walking are needed to investigate whether obese individuals adopt novel energy saving mechanisms during walking.     

Background ventilatory stimulus as a determinant of load compensation

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.     

Effects of age and physical activity status on the speed-aerobic demand relationship of walking.

Older adults tend to show lower preferred walking speeds and higher aerobic demands per distance walked than young adults. It has been suggested that a more sedentary life-style contributes to diminished musculoskeletal functioning, which in turn contributes to poorer economy of motion in the aged and sedentary adults. The purpose of this study was to quantify the speed-aerobic demand relationship during walking for old (greater than 65 yr of age) and young adults and to determine whether physical activity status affects this relationship. Aerobic demands for 30 young and 30 old individuals representing sedentary and physically active groups were measured as the subjects performed treadmill walking at seven speeds ranging from 0.67 to 2.01 m/s. All four age/physical activity groups displayed U-shaped speed-aerobic demand curves with minimum gross oxygen consumption per unit distance walked (ml.kg-1.km-1) at 1.34 m/s. A statistically significant age effect on walking aerobic demand was observed, with old subjects showing an 8% higher mean aerobic demand than the young subjects. This age-related effect was not associated with shifts in the speed at which aerobic demand was minimized or with the preferred walking speed of older individuals falling on a less economical portion of the speed-aerobic demand curve. Rather, it was speculated that declines in force-generating capacity of muscle in the aged may require recruitment of additional motor units and perhaps an additional proportion of less economical fast twitch muscle fibers to generate necessary forces. Physical activity status had no significant effect on walking aerobic demand.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological responses to prolonged treadmill walking with external loads

Limited information is available regarding the physiological responses to prolonged load carriage. This study determined the energy cost of prolonged treadmill walking (fixed distance of 12 km) at speeds of 1.10 m.s-1, 1.35 m.s-1, and 1.60 m.s-1, unloaded (clothing mass 5.2 kg) and with external loads of 31.5 and 49.4 kg. Fifteen male subjects performed nine trials in random order over a 6-week period. Oxygen uptake (VO2) was determined at the end of the first 10 min and every 20 min thereafter. A 10-min rest period was allowed following each 50 min of walking. No changes occurred in VO2 over time in the unloaded condition at any speed. The 31.5 and 49.4 kg loads, however, produced significant increases (ranging from 10 to 18%) at the two fastest and at all three speeds, respectively, even at initial exercise intensities less than 30% VO2max. In addition, the 49.4 kg load elicited a significantly higher (P less than 0.05) VO2 than did the 31.5 kg load at all speeds. The measured values of metabolic cost were also compared to those predicted using the formula of Pandolf et al. In trials where VO2 increased significantly over time, predicted values underestimated the actual metabolic cost during the final minute by 10-16%. It is concluded that energy cost during prolonged load carriage is not constant but increases significantly over time even at low relative exercise intensities. It is further concluded that applying the prediction model which estimates energy expenditure from short-term load carriage efforts to prolonged load carriage can result in significant underestimations of the actual energy cost.     

Effects of moderate external loading on the aerobic demand of submaximal running in men and 10 year-old boys

The effects of moderate external loading on the aerobic demand of submaximal running were studied in habitually active adult men (29-37 yrs) and 10 year-old boys. The load was symmetrically placed around the trunk and adjusted to correspond to 10% of body weight. Running was performed on a treadmill at 8, 10 and 11 km X h-1 (2.2, 2.8 and 3.1 m X s-1). A small, but consistent decrease in net oxygen uptake (gross oxygen uptake in ml X kg-1 X min-1 minus calculated basal metabolic rate) with load was observed in both groups at all speeds, except for the men at 8 km X h-1. The decrease was larger for the boys and tended to enhance with speed. The boys had a higher net oxygen uptake than the adults at all unladen running velocities, whereas the difference in the loaded condition was significant only at the highest speed. The decrease in net oxygen uptake with load could not be directly correlated with differences in body weight or step frequency. It is hypothesized that a difference in the utilization of muscle elastic energy could underlie part of the age and load dependent changes observed in running economy.     

Detection of inspiratory resistive loads in double-lung transplant recipients.

The afferent pathways mediating respiratory load perception are still largely unknown. To assess the role of lung vagal afferents in respiratory sensation, detection of inspiratory resistive loads was compared between 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects. Despite a similar unloaded and loaded breathing pattern, the DLT group had a significantly higher detection threshold (2.91 +/- 0.5 vs. 1.55 +/- 0.3 cmH(2)O. l(-1). s) and Weber fraction (0.50 +/- 0.1 vs. 0.30 +/- 0.1) compared with the Nor group. These results suggest that inspiratory resistive load detection occurs in the absence of vagal afferent feedback from the lung but that lung vagal afferents contribute to inspiratory resistive load detection response in humans. Lung vagal afferents are not essential to the regulation of resting breathing and load compensation responses.     

Himalayan porter's specialization: metabolic power, economy, efficiency and skill

Carrying heavy loads in the Himalayan region is a real challenge. Porters face extreme ranges in terrain condition, path steepness, altitude hypoxia and climate for 6-8h a day, many months a year, since they were boys. It has been previously shown that, when carrying loads on level terrain, porters' metabolic economy is higher than in Caucasians but the reasons are still unknown. We monitored Nepalese porters both during 90 km trekking in Khumbu Valley and at two different altitudes (3490 and 5050 m above sea-level), where they were compared to Caucasian mountaineers during (22%) gradient walking. Both subject groups carried a load of up to 90% body mass. The remarkably higher performance of porters during uphill locomotion (+60% in speed, +39% mechanical power) is only partly explained by the lower cost of loaded walking (-20%), being also the result of a better cardio-circulatory adaptation to altitude, which generates a higher mass-specific metabolic power (+30%). Consequently, Nepalese porters show higher efficiency, both during uphill and downhill loaded walking. Their higher economy on steep paths cannot be ascribed to a better exchange between potential and kinetic energy, as in our experiments the body centre of mass travelled monotonically uphill (or downhill). A different oscillation pattern of the loaded head-trunk segment, together with the analysis of the different components of the mechanical work during load carrying, suggests that achieved motor skills in balancing the loaded body segment above the hip could play a role in determining the better economy of porters.     

What are the relations between mechanics, gait parameters, and energetics in terrestrial locomotion?

Are the different energy-conserving mechanics (i.e., pendulum and spring) used in different gaits reflected in differences in energetics and/or stride parameters? The analysis included published data from several species and new data from horses. When changing from pendulum to spring mechanics, there is a change in the slope of metabolic rate (MR) vs. speed in all species, in birds and quadrupeds there is no step increase, and in humans there are conflicting reports. At the trot-gallop transition, where quadrupeds are hypothesized to change from spring mechanics to some combination of spring and pendulum mechanics, there is a change in slope of MR vs. speed in horses but not in other species. Stride frequency (SF) is a logarithmic function of walking speed in all species, a linear function of trotting/running speed, and nearly independent of speed in galloping. In humans and horses there is a discontinuity in SF at the walk-trot (run) transition but not in birds. The slope of time of contact vs. speed does not change with mechanics in most species, but it does in humans. In horses and humans, there is a discontinuity at the walk-trot (run) transition and data for other species do not permit generalization. Duty factor (DF) in humans is greater than 0.5 in walking (pendulum mechanics) and less than 0.5 when running (spring mechanics). However, this is not true in many species that have DF>0.5 at the lowest speeds where they use spring mechanics. When trotting at low speeds, horses use forelimb DF>0.5 and hind limb DF<0.5. Thus, it is confusing to distinguish between walking and running by DF.     

Effect of theophylline on the velocity of diaphragmatic muscle shortening

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two-stage optimization process for formulation of chitosan microspheres

The objective of the present study was to optimize the concentration of a chitosan solution, stirring speed, and concentration of drugs having different aqueous solubility for the formulation of chitosan microspheres. Chitosan microspheres (unloaded and drug loaded) were prepared by the chemical denaturation method and were subjected to measurement of morphology, mean particle size, particle size distribution, percentage drug entrapment (PDE), drug loading, and drug release (in vitro). Morphology of the microspheres was dependent on the level of independent process parameters. While mean particle size of unloaded microspheres was found to undergo significant change with each increase in concentration of chitosan solution, the stirring rate was found to have a significant effect only at the lower level (ie, 2000 to 3000 rpm). Of importance, spherical unloaded microspheres were also obtained with a chitosan solution of concentration less than 1 mg/mL. Segregated unloaded microspheres with particle size in the range of 7 to 15 microm and mean particle size of 12.68 microm were obtained in the batch prepared by using a chitosan solution of 2 mg/mL concentration and stirring speed of 3000 rpm. The highest drug load ( microg drug/mg microspheres) was 50.63 and 13.84 for microspheres containing 5-fluorouracil and methotrexate, respectively. While the release of 5-fluorouracil followed Higuchi's square-root model, methotrexate released more slowly with a combination of first-order kinetics and Higuchi's square-root model. The formation of chitosan microspheres is helped by the use of differential stirring. While an increase in the concentration of water-soluble drug may help to increase PDE and drug load over a large concentration range, the effect is limited in case of water-insoluble drugs.     

Faster top running speeds are achieved with greater ground forces not more rapid leg movements.

We twice tested the hypothesis that top running speeds are determined by the amount of force applied to the ground rather than how rapidly limbs are repositioned in the air. First, we compared the mechanics of 33 subjects of different sprinting abilities running at their top speeds on a level treadmill. Second, we compared the mechanics of declined (-6 degrees ) and inclined (+9 degrees ) top-speed treadmill running in five subjects. For both tests, we used a treadmill-mounted force plate to measure the time between stance periods of the same foot (swing time, t(sw)) and the force applied to the running surface at top speed. To obtain the force relevant for speed, the force applied normal to the ground was divided by the weight of the body (W(b)) and averaged over the period of foot-ground contact (F(avge)/W(b)). The top speeds of the 33 subjects who completed the level treadmill protocol spanned a 1.8-fold range from 6.2 to 11.1 m/s. Among these subjects, the regression of F(avge)/W(b) on top speed indicated that this force was 1.26 times greater for a runner with a top speed of 11.1 vs. 6.2 m/s. In contrast, the time taken to swing the limb into position for the next step (t(sw)) did not vary (P = 0.18). Declined and inclined top speeds differed by 1.4-fold (9.96+/-0.3 vs. 7.10+/-0.3 m/s, respectively), with the faster declined top speeds being achieved with mass-specific support forces that were 1.3 times greater (2.30+/- 0.06 vs. 1.76+/-0.04 F(avge)/ W(b)) and minimum t(sw) that were similar (+8%). We conclude that human runners reach faster top speeds not by repositioning their limbs more rapidly in the air, but by applying greater support forces to the ground.     

The metabolic cost of changing walking speeds is significant,implies lower optimal speeds for shorter distances,and increases daily energy estimates

Humans do not generally walk at constant speed, except perhaps on a treadmill. Normal walking involves starting, stopping and changing speeds, in addition to roughly steady locomotion. Here, we measure the metabolic energy cost of walking when changing speed. Subjects (healthy adults) walked with oscillating speeds on a constant-speed treadmill, alternating between walking slower and faster than the treadmill belt, moving back and forth in the laboratory frame. The metabolic rate for oscillating-speed walking was significantly higher than that for constant-speed walking (6–20% cost increase for ±0.13–0.27 m s⁻¹ speed fluctuations). The metabolic rate increase was correlated with two models: a model based on kinetic energy fluctuations and an inverted pendulum walking model, optimized for oscillating-speed constraints. The cost of changing speeds may have behavioural implications: we predicted that the energy-optimal walking speed is lower for shorter distances. We measured preferred human walking speeds for different walking distances and found people preferred lower walking speeds for shorter distances as predicted. Further, analysing published daily walking-bout distributions, we estimate that the cost of changing speeds is 4–8% of daily walking energy budget.     

Physiological cost of running while wearing spring-boots

The purpose of the study was to investigate the physiological cost of running in spring-boots compared with running in running shoes at different speeds. During testing, subjects (n = 7) completed running trials while wearing spring-boots and running shoes. Three speed conditions (2.23, 2.68, and 3.13 m.s(-1)) were completed per shoe condition (i.e., spring-boots and running shoes). Rate of oxygen consumption (Vo(2)), heart rate (HR), rating of perceived exertion (RPE), and stride frequency were recorded for each condition. Order of shoe conditions was balanced, with speeds tested continuously from slow to fast. There was no difference in Vo(2), HR, or RPE between shoe conditions across speeds (p > 0.05). Stride frequency was lower during running in spring-boots vs. running shoes at each speed (speed of spring-boots vs. running shoes for 2.23 m x s(-1): 69.9 +/- 2.9 strides x min(-1) vs. 75.6 +/- 3.5 strides x min(-1); for 2.68 m x s(-1): 71.3 +/- 5.2 strides x min(-1) vs. 79.4 +/- 5.0 strides x min(-1); for 3.13 m x s(-1): 73.6 +/- 7.3 strides x min(-1) vs. 83.1 +/- 8.2 strides x min(-1); p < 0.05). Despite the added mass to the lower extremity and change in stride frequency during running in spring-boots, the physiological cost of running was similar to that of running in running shoes. Exercising while running in spring-boots may provide less impact force with no change in running economy.     

Effect of elastic loading on ventilatory pattern during progressive exercise

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.     

Modulation of force transmission to the head while carrying a backpack load at different walking speeds

This study was designed to investigate the capability of the joints and segments to reduce transmission of forces during load carriage. Eleven subjects were required to carry a backpack loaded with 40% of their body weight and to walk at 6 speeds increasing from 0.6 to 1.6 ms(-1) in increments of 0.2 ms(-1), and then decreasing in the same manner. Subjects were filmed in 3-dimensions, but analysis of shock transmission ratio (TR) was limited to the sagittal plane. Shock transmission was measured as the ratio of peak vertical accelerations (ankle:head, ankle:knee, and knee:head) measured immediately following foot strike. TR for all ratios increased significantly as a function of increasing speed. TR from the ankle to the head showed no significant increase as a function of load carriage, but did increase as a function of load in transmission from knee to head. A significant interaction effect revealed that during load carriage at the higher speeds the acceleration of the ankle and knee decreased below that for the unloaded conditions. These findings suggest that the potentially injurious effects of previously observed increased ground reaction forces and increased joint stiffness while walking with loads are offset by adaptations in the gait pattern that maintain force transmission at acceptable levels. Increased variability in the acceleration of the head and in the transmission ratios suggest a potentially destabilizing effect of load carriage on the head trajectory.     

How do load carriage and walking speed influence trunk coordination and stride parameters?

To determine the effects of load carriage and walking speed on stride parameters and the coordination of trunk movements, 12 subjects walked on a treadmill at a range of walking speeds (0.6-1.6 m s(-1)) with and without a backpack containing 40% of their body mass. It was hypothesized that compared to unloaded walking, load carriage decreases transverse pelvic and thoracic rotation, the mean relative phase between pelvic and thoracic rotations, and increases hip excursion. In addition, it was hypothesized that these changes would coincide with a decreased stride length and increased stride frequency. The findings supported the hypotheses. Dimensionless analyses indicated that there was a significantly larger contribution of hip excursion and smaller contribution of transverse plane pelvic rotation to increases in stride length during load carriage. In addition, there was a significant effect of load carriage on the amplitudes of transverse pelvic and thoracic rotation and the relative phase of pelvic and thoracic rotation. It was concluded that the shorter stride length and higher stride frequency observed when carrying a backpack is the result of decreased pelvic rotation. During unloaded walking, increases in pelvic rotation contribute to increases in stride length with increasing walking speed. The decreased pelvic rotation during load carriage requires an increased hip excursion to compensate. However, the increase in hip excursion is insufficient to fully compensate for the observed decrease in pelvis rotation, requiring an increase in stride frequency during load carriage to maintain a constant walking speed.     

Effect of resistive loading on ventilatory response to hypoxia.

Ventilatory responses to hypoxia, with and without an inspiratory resistive load, were measured in eight normal subjects, using a rebreathing technique. During the studies, the end-tidal P-CO2 was kept constant at mixed venous level (Pv-CO2) by drawing expired gas through a variable CO2-absorbing bypass. The initial bag O2 concentration was 24% and rebreathing was continued until the O2 concentration in the bag fell to 6% or the subject's arterial oxygen saturation (Sa-O2), monitored continuously by ear oximetry, fell to 70%. Studies with and without the load were performed in a formally randomized order for each subject. Linear regressions for rise in ventilation against fall in Sa-O2 were calculated. The range of unloaded responses was 0.78-3.59 1/min per 1% fall in Sa-O2 and loaded responses 0.37-1.68 1/min per 1% fall in Sa-O2. In each subject, the slope of the response curve during loading fell by an almost constant fraction of the unloaded response, such that the ratio of loaded to unloaded slope in all subjects ranged from 0.41 to 0.48. However, the extrapolated intercept of the response curve on the Sa-O2 axis did not alter significantly indicating that the P-CO2 did not alter between experiments. These results suggest that the change in ventilatory response to hypoxia during inspiratory resistive loading is related to the mechanical load applied, with the loaded slope being directly proportional to the unloaded one.