Effects of hyperoxia metabolism during

on leg blood flow and exercise

HUGH G. WELCH, FLEMMING BONDE-PETERSEN, TERRY GRAHAM, KLAUS KLAUSEN, AND NIELS SECHER Laboratory for the Theory of Gymnastics, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark

HUGH G., FLEMMING BONDE-PETERSEN, TERRY KLAUS KLAUSEN, AND NIELS SECHER. Effects of hyperoxia on leg blood flow and metabolism during exercise. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42(3): 385-390, 1977. -These experiments were designed to investigate the effects of 0, breathing on limb blood flow and metabolism during exercise. Six subjects took part in the study. Four subjects breathed air or 100% O2 while pedaling a Krogh bicycle at 150 W (5570% of maximal aerobic capacity). Two subjects breathed either 60% or 100% 0, while working at a power output at or slightly in excess of their maximal aerobic capacities. The major findings of the study were 1) leg blood flow is reduced during exercise when comparing hyperoxia with normoxia; 2) ire, of the exercising limb is not different during hyperoxia; 3) 0, delivery to the leg (the product of blood flow and arteriovenous 0, difference) is not significantly different in the two conditions; and 4) blood pressure is not markedly affected in the experiments at 150 W. Since BP was not different during hyperoxia, at a time when flow was reduced by 1 l%, this suggests an increased resistance to flow in the exercising limb. In general, these findings are consistent with those reported for in situ dog muscle but are at variance with results of experiments with humans, especially the reports indicating substantial increases in 0, uptake during hyperoxic conditions.

to investigate the circulatory and metabolic responses of exercising leg muscles during hyperoxia.

WELCH,

GRAHAM,

0.) breathing; 0, uptake

blood gases; blood lactate;

exercise

METHODS

Six young males took part in the study. All six were physical education students at the University of Copenhagen and were regularly active. They volunteered to participate and were accepted only after reading and signing a statement regarding the risks involved, their rights, and the conditions of payment. BZood fZow. Blood flow in the exercising limbs was measured by a dye-dilution technique, as described by Jorfeldt and Wahren (12). This involves a constant infusion of indocyanine green dye (Cardio-Green) into the femoral artery of one leg with simultaneous venous sampling from the two femoral veins. Differences in venous dye concentrations are inversely related to leg blood flow which can be calculated from the dilution factor and the rate of dye infusion (see (12) for further details). The subjects arrived early in the morning after a light breakfast for percutaneous introduction of catheters during local anesthesia. The blood vessels were punctured-2-3 cm distal to the inguinal ligament. The venous catheters were commercial1 .y available ones (Intracath) ; the arterial catheter was prepared from 400-mm lengths of thin (1.8~mm) Teflon tubing. The outer diameter of the Teflon tubing matched that of the puncture needle; this was important in order to avoid arterial bleeding. Plastic stopcocks were connected to the venous catheters and a metal stopcock (Ole Dich) to the arterial catheter. All catheters were introduced deeply in the central direction in the artery and in the veins and later retracted leaving exactly 100 mm in the vessels. The position of the catheters was secured with adhesive tape and Nobecutane spray (Bofors). After each experiment the position was rechecked to ensure that the catheters had not moved. This is of vital importance for the reliability of the method. Usually the arterial catheter was placed in the right side, but in two cases, the left a. femoralis was used. During the periods of leg flow measurement, indocyanine green dissolved in isotonic saline (1 mg ml+> was infused through the femoral artery catheter at a rate of

hyperemia;

WHEN THE OXYGEN PRESSURE (Po2) of inspired air is varied, maximal 0, uptake (Vo, max) and performance in exhaustive exercise are reported to increase or decrease in parallel (1, 6, 7, 16). This has led to the belief that a causal relationship exists between the 0, supply and the variation in performance. However, in experiments with in situ dog gastrocnemius muscle, no increase in Voz or in maximal tension can be demonstrated during hyperoxia, even when the muscle is stimulated at supramaximal levels (19; Wilson and Stainsby, unpublished observations). There is very little information in the literature regarding the effects of hyperoxia on the metabolism of working muscles in humans. Recent advances in the techniques for estimating peripheral blood blow in humans (12) make it possible to study in a more quantitative way the responses of active muscle groups to exercise. We have used this technique in the present study

l

385

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386

WELCH

approximately 1.9 ml min+ using a Harvard infusion pump. The system was regularly calibrated to ensure accurate infusion rates. After 60-90 s of infusion, the sampling of venous blood from the infused and noninfused legs was started. Four samples of 4 ml were drawn from each vein into plastic syringes during a period of 50-60 s. After taking a small portion for hematocrit determination, the remainder of the sample was centrifuged and plasma dye concentration was read on a Zeiss spectrophotometer against blank samples obtained prior to infusion. In no case was lipemic plasma observed. BZood samples. Samples were drawn from the arterial catheter and the contralateral venous catheter simultaneously at prescribed times before and during exercise, for determination of blood gas concentration (Van Slyke) and for lactate and glucose concentration (both determined enzymatically; modifications of the Boehringer kit). Expired air was collected in plastic Douglas bags at regular intervals for determination of minute ventilation (VE), Vo2, and VCO~ (except that Vo, could not be determined during hyperoxia). Air volumes were measured with a balanced Tissot spirometer and 0, and CO, gas fractions with a paramagnetic (Servomex OA 184) and an infrared (Beckman LB-l) analyzer, respectively. The analyzers were calibrated each time against cylinders of gas, the contents of which were periodically checked with conventional Scholander gas analysis. Blood pressure and heart rate. Systolic/diastolic blood pressures and heart rate were registered with a Statham pressure transducer connected to the femoral artery catheter. The signal from the transducer was registered via a strain-gauge bridge (Peekel 581 DHL) to a strip chart recorder (Brush Mark 220). In the Op-breathing experiments, the subject inhaled from a 200-liter rubber Douglas bag containing water, which was flushed continuously with 0, from a pressure l

WORK

LEG

RATE

(WATTS)

BLOOD

DOUGLAS

cylinder. The use of the bag ensured a stable inspired gas fraction and permitted the humidification of the dry air from the cylinder. Design. Two sets of experiments were conducted on the Krogh bicycle ergometer, one at 150 W and one at more strenuous exercise. The lower exercise power corresponded to about 55-70% of maximal aerobic power and was chosen to provide data comparable to that available for both normoxic and hyperoxic conditions (2, 20). This rate of work could be continued for the desired period in all of our subjects. The higher rates of work were used to investigate possible changes that could be ascribed in general to the conditions during strenuous exercise, but still a level was chosen that could be sustained for a long enough time to create at least a “quasi-steady state.” These rates of work represented about 95-110% of VO, max for the two subjects involved in this series. Exercise at 150 W. Four subjects took part in this series. The subject came into the laboratory early in the morning. The catheters were introduced and filled with heparinized isotonic saline, which was also used to flush the catheters during the experiment. The subject then rested for 30 min in the supine position before mounting the ergometer. He began by pedaling for 10 min at 60 rpm with no resistance on the flywheel while breathing either room air or 100% 0,. This period permitted the subject to equilibrate with the gas mixture while we checked the catheters and took baseline measurements. At the end of 10 min, the electric brake of the bicycle was switched on, and the subject rode at 150 W for 20 min. At prescribed times (Fig. l), samples were drawn for the various cardiovascular and metabolic determinations. This was performed two times during the steady state of each exercise period to collect double measurements. On completion of the 20-min period, the resistance was removed from the flywheel and the subject continued to pedal at 60 rpm at zero load. He did so for 1

I

0

150

FLOW

LACTATE,

BLOOD

I

GLUCOS

FIG. 1. Protocol for the experiments at 150 W. First 10 min represents a period of no-load cycling. Solid bars represent the sampling periods for the respective measurements. “Heavy” work experiments are explained in the text.

GASES

BAGS

\

TIME

ET AL.

.

(MINUTES)

I

0

IO

1

I

1

I

20

I

I

1

30

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BLOOD

FLOW

AND

METABOLISM

DURING

EXERCISE

IN

another 10 min following the switch to the other gas. He then repeated the entire 20-min procedure at 150 W with samples taken at similar periods. To ensure that the order of the gases did not alter the results, each subject returned to the laboratory 3-4 wk later and repeated the experiment, using the gases in reverse order. Thus we obtained at least four separate estimates (two pairs of double measurements) of each variable with each gas mixture. The order of the gases in the first ride was randomized. Heavy exercise. Two different subjects participated in this series. We also utilized 60% 0, as well as 100% in these experiments. As in the previous series the subjects rode for 10 min breathing either room air or the hyperoxic gas with no resistance on the flywheel. After this the resistance was increased to a point such that the effort required was just less than that required to elicit . The subjects rode at this rate (200 and 265 W, vo respectively) for 10 min, measurements being taken during the last 2-4 min. Then the load was increased to a “supramaximal” level (235 and 300 W, respectively) for 5-6 min, the measurements being repeated at the end of this period. This brought the subject to complete exhaustion. After 30-60 min of recumbent rest the experiment was repeated with the subject breathing the other gas. About 2 wk later, the subject returned to the lab and repeated the experiment with the gases in reverse order. 2

tnax

387

HYPEROXIA

l

RESULTS

Analysis of the data indicated that the order in which the gases were utilized had no effect except for some minor variation in the case of the lactate data. The final statistical analysis was therefore performed as a comparison between values for air and 0, at equivalent times on the same day. For example, the value for leg blood flow at 7 min during air breathing was paired with the 7-min value during 0, breathing on that same day. During the subject’s subsequent test with the gas order reversed, the 7-min values for 0, and for air on that day were paired. The data could then be analyzed with a two-way analysis of variance with paired comparisons. The experiments performed during the heavy exercise power were too few in number to be treated statistically as pairs, but where it was appropriate these data were incorporated with the 150-W data for graphical display. Table 1 summarizes the results of the study. The leg blood flow is consistently lower during hyperoxia than normoxia (see also Fig. 2). For the 150-W experiments the average reduction is 11% and is statistically significant. The result of this is that, despite a 10% increase in arterial 0, concentration (C&J with hyperoxia, the 0, delivery to the leg (Q x C%,) is not different in the two conditions. The VO, for the legs is not significantly different when the subject breathes air or 0, at 150 W. Similarly, the VCO~ of the legs is not different, and the calculated RQ values are virtually identical. The Vo, calculated for two legs was consistently between 70-80% of the pulmonary Vo, (X = 76%). C%Z was significantly higher with

TABLE

1. Summary

table 150 w

Variable Leg blood flow: l-leg, 1. min-’ artery, C&t,, : femoral ml. 1-l cvtr,: femoral veins, ml. 1-l a-v 0, diff, ml. 1-l Leg 0, uptake: l-leg, 1. min-’ cv,+: femoral vein, ml. 1-l C&Y, : femoral artery, ml-l-’ v-a CO, diff, ml. 1-l Leg CO, output: l-leg, lemin ’ RQ: leg 0, delivery (flow * Cq,,), 1. min-’ VE BTPS, 1. min-’ Pulm 0, uptake, lemin I Pulm CO, output, 1* min--’ Heart rate, beats. min- 1 Systolic BP, Torr Diastolic BP, Torr Arterial lactate, mm01 -1-l Lactate release, mmol.min ’ (flow * v-a dim

n 14

Air 5.5

200-300

w

P 02 4.9

?l

co.01

10

Air 7.3

02 6.8

15

198

217

Effects of hyperoxia on leg blood flow and metabolism during exercise.

Effects of hyperoxia metabolism during on leg blood flow and exercise HUGH G. WELCH, FLEMMING BONDE-PETERSEN, TERRY GRAHAM, KLAUS KLAUSEN, AND NIELS...
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