27
CARBON DIOXIDE TOLERANCE STUDIES H. A. GLATTE, JR., Captain, USAF, MC G. J. MOTSAY, Captain, USAF, MC B. E. WELCH, Ph.D.

CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

  • Upload
    others

  • View
    2

  • Download
    0

Embed Size (px)

Citation preview

Page 1: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

CARBON DIOXIDE TOLERANCE STUDIES

H. A. GLATTE, JR., Captain, USAF, MC

G. J. MOTSAY, Captain, USAF, MC

B. E. WELCH, Ph.D.

Page 2: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

L

FOREWORD

This work was done in the Environmental Systems Branch under AF task No. 793002and NASA contract No. T-41829-G. The atudy was accomplished during 1966, andthe paper was submitted for publication on 14 June 1967.

The cardiotrchometer used in this study was constructed in the BiomedislEngineering Branch.

This report has been reviewed and is approved.

Colonel, Us", MCCommander

Page 3: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

ABSTRACT

Seven normal volunteers were eixposed to an environment of 21 Mm. H9 CO2 (3%)for a 5-day experimental period bracketed by two 5-day control periods. Measurementsincluded daily serum and urine electrolytes, blood gas studies, and net acid excretionstudies. Also included were detailed investigations of respiratory physiology, exerciseresponse, and psychomotor performance. All subjects tolerated the experimentalatmoisphere wtnoundue problems. Arterial and alveolar PcO2's increased 3 to 4cumo. Hg with a mild reduction in arterial pH from 7.40 to 7.37. Arterial pH valuesreturned to near control values by the fourth day. No increases were noted in netacid excretion. Exercise was tolerated remarkaby well.

iI

Il

Page 4: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

ii

A DIOXIDE TOLAN STUDIO

L INTRODUCTION described and some of the data (acid-basechanges) disagree with most reports in the

With the advent of submarine and aero- literature. A very extensive psychomotorspace research, the problems of carbon dioxide program of testing failed to reveal any per-removal and man's ability to perform adequate- formanue degradation. Earlier stuuies by thisly in varying levels of carbon dioxide have group at levels of 21 to 23 mm. Hg ambientbecome paramount. Numerous studies have PCo2 (3%7) showed some changes in psycho-been carried out in man with acutely elevated motor performance (39). These changes arelevels of carbon dioxide (2, 4, 6, 20, 25). Owing questioned at this time as no adequate controlsto obvio'us problems, studies of man in chron- were available, and there was no ktnowledge ofica!!y elevated carbon dioxide environments possib!e contaminant buildup which could haveare less numerous. greatly influenced the results. A 4-day study

by Cutler and associates (5) at the same levelProblems of importance to the aerospace of carbon dioxide failed to reveal any per-

investigator in studying chronic hypercapnia formance degradation. Two other studies havepertain mainly to respiratory, acid-base, and been conducted by the Russians, who reportedpsychomotor performance parameters. A brief them in a very incomplete manner (59). Thus,r6sum6 of manned expexience in chronically owing to the paucity of chronic data available,elevated levels' of carbon dioxide is presented the need fcr more comprehensive carbonin table I. These studies comprise the sum dioxide investigations is obvious.total of chronic CO2 exposure utilizing normalman as test sub~jects. Several of these studies The following study was designed to pro-by Schaefer and coworkers (38, 44, 45, 47) have vide additional data in this area by determiningbeen carried out in submarine environments the effects of 21 mm. Htg ambient Pca. 'inwith one of 42 days' duration being conducted normal man. An effort was made to assessat 12 mm. Hg ambient Pco_ (1.5%). Many acid-base metabolism with th• bestavbilableof the aspects of this study were excellent; methodology, which will be reported ip detail.however, methodology was not adequately The opportunity was also taken to study

psychomotor performance. In addition, ex-

TABLE I ercise studies were carried out with simulta-neous simple reaction control and memory

Chronic hypercapnia studies tasks to give some insight into psychomotorperformance with exercise.

-% Duration'CO( (%) Pc°2 (days) nestigatorMMARY

1.0 7-8 30 Russia (59)1.0 1 30 .S. Navy (8) Seven normal male volunteers have success-" 2.0" 1-5 30 Russa (59) fully lived for a period of 5 days in a space3.0 21 i 5 U.S..ir Force 5 cabin simulator with an ambient IPco 2 ofS4.0 I31 I 5 U.S. Air Force (14) 21 mm. Hg W37 CO- at sea level). Physiclogic52 38 3-4 U.S. Navy (3) studies indicated that the atmosphere was only

o1

Page 5: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

a mild chali-nge to acid-base adaptive mecha- subjects' vital statistics. The study wasnisms. Induced respiratory acidosis was al- originally planned for 8 subjects; howev-.r, dur-most completely compensated by the fourth to ing the control period of the first study,fifth day. No subject showed evidence of a 1 subject with acute tonsillitis had to be re-prolonged uncompensated acidosis. Minute moved from the chamber.ventilation w.ms increased approximately 2.5liters/min. along with a 3 to 4 mm. Hg eleva- After selection, the subjects underwent ation in arter.al and alveol2r PCee. This was detailed hitory, pl-ysical examination, postero-easily tolerated. No abnormalities were noted anterior and lateral chest x-rays, and 12-leadin pulmonary function testing. There was no electrocardiogram. Before final selection, allsuggestion of abnormalities of mineral metab- candidates hnd a detailed survey of blood andolism. Serum and urine calcium and phos- urine chemistries. Metabolic and acid-base de-phorus remained normal. Hlydroxyproline terminations are listed in table MI. Table IVstudies failed to denote abnormal parathyroid lists liver function, hematology, and renalactivity. A full hour of moderate exercise was studies performed.carried out several times during the study.These exercise periods were always completedand tolerated well. Repetitive psychomotor These studies were conducted in a 4-manand psychologic testing was done daily. No space simulator altitude chamber at the USAFdecrements were noted in any of these studies School of Aerospate Medicine. Carbon dioxideand would indicate that the CO2 atmosphere was monitored by a Beckman L-R-1 infraredhad no adverse effects. It was concluded that C0 2 analyzer; oxygen, by a Beckman F-3a 5-day exposure to 3% CO2 was easily adapted analyzer; and nitrogen, by a Med-Scienceto and failed to adversely affect moderate ex- nitralyzer 300 AR. Calibration of all instru-ercise ability, psychomotor performance, or mepts was carried out every 12 hours by usemineral metabolism, of standards verified by gas chromatography.

Readings were taken every 15 minutes. Table Vlists the average environmental conditions dur-

HL MATERIALS AND METHODS ing both phases of this study, which wasbroken down into substudies I and 1L

Study format

All 7 subjects were normal airmen volun- The volunteer subjects in the two groupsteers selected from dne Lackland AFB Basic were studied for 15 days while living in theTraining Facility. They were selected after space simulator. The study plan was outlinedan interview with the principal investigator as follows: control, 5 days; experimental,and review of past records. Table II lists the 5 days; and recovery, 5 days.

TABLE II

Vital statistics of subjects

It[ H Height Weight Surface areaIi Subject No Age (in.) (Tb.) (r. 2) Education

D. H. 1 19 1 71 198 2.11 High school graduateR. L. 2 I 21 71 158 1.91 2 years of collegeC.O. 3 19 71 1 160 1.92 1% years of collegeT. A. 4 [ 18 64 129 1.62 High school graduateA. C. 5 19 71½ 161 1.94 2 years of collegeD. K. 6 19 73 155 1.92 High school graduateK. S. 7 ' 23 71½ 1. 186 2.05 C-llege graduate

2

Page 6: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

TABLE III

Metabolic studies

Blood )a. Venous Na, K, C", C0 2, Ca, Mg, P, creatin'ne Dailyb. "Arterialized" Pco2. pH on capillary blood

Urinea. Na, K, Cl, Ca, Mg, P, creatinineb. NH 4+, HCO3 -, .itratable acidity, pH 24-hr. excretionc. 24-hour hydrogen ion excretion

NH4 + + T. A. - HCO3 - - 24 H + excretion

TABLE IV normal alveolar Po2's (9). In this manner, theonly experimental variable w*.s elevated carbon

Miscellaneous studies dioxide.

Liver function The transition from low to high CO2 partialBilirubin pressures occurred over a 6-hour period from

D~ireci 0200 to 0800 hours while the subjects wereIndirect sleeping. The subjects were not told when the

SGOT carbon dioxide was increased.SGPTAlkaline phosphatase To insure a stable, steady-state excretionTotal protein of hydrogen ion and electrolytes, the subjectsSerum protein electrophoretic study ate a prepared liquid diet (SMBP-D-10) which

Hematology contained approximately 2,600 calories and wasHemoglobin adequate in carbohydrates, fats, and protein.Hematocrit The diet also provided approximately 100 mEq.Red blood cell count NaCl per day and 30 mEq. K- per day.Red cell morphologyWhite blood cell count with differential Figure 1 is a schedule of the daily activitiesReticulocyte count throughout the test. On the 6 days of exercise

Renal studies, psychomotor testing hours wereBUN changed. Two exercise studies were performedSerum creatinine irn the morning and two immediately afterUrine creatinine

Creatir:ine clearance lunch. Exercise was completed by 1500 hours.Renal sediment examUrine culture Blood studies

Free-flowing venous blood samples wereTo assure a seal on the chamber, the entire drawn from antecubital veins daily during the

study was carried out at a total pressure of fasting period. Determinations included Na+,700 mm. Hg. During the control phases of the K-, C1-, total CO2 , Cal -, Mg+ F, P, andstudy the partial pressure of carbon dioxide creatinine. Serum Na-, K i-, creatinine, and(Pco2 ) was nominal, while during the experi- phosphate were determined using automatedmental phase the ambieist Pcom was maintained technics (11, 16, 56). A Cotlove titrator wasat 21 mm. Hg. Because of the known stimula- utilized for serum ,chorides, and total CO2 wastory effect the elevated PcO2 has on respira- determined by the automated method oftory minute volume, the partial pressure of Skeggs (52). Initially, samples were split andoxygen (P02) was reduced during the experi- total CO.! was compared with this proceduremental phase of the study in order to maintain carried out in the classic Van Slyke manometric

3

4.

Page 7: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

TAPILE V

Environmental conditionw (period meas)

_ _ _ _ _ _ _ _ _ _ S tu dy I S tu dy II

Cont. I Exp. Coat. 2 Cont. 1 Exp. Cont. 2Total pressure (mm. Hg) 699.2 699.6 699.2 699.3 699.9 699.7P02 (mm. Hg) 167.4 136.1 156.7 157.0 136.2 156.3

Pco2 (rnnL H9) 4.4 21.4 1.6 2.1 21.4 1.3

PN2 (mm. Hg) 540.5 535.6 .5-1 546.4 544.4 549.7

Temperature (' C.) 22.7 i 23.2 23.3 22.9 22.1 22.9

Relative humidity (%) 48.3 j 46.7 47.6 49.7 53.7 52.0

SUBJECT #1 SUBJECT #2 SUBJECT #3 SUBJECT #4

0730 ------------ Basal Respiratory Studies ------------------0800 ----------------------- EKG ------------------------------0830 ------------------ Blood Studies ------------------------

------------------- Liquid Diet -------------------------

0900 Psychomotor Testing0930 Psychomotor Testing1000 Psychomotor Testing1.030 Psychomotor Testing1100 --------------------- Hygiene-------------------------1200 -------------------- Liquid Diet ..............1300

1400 Psychomotor Testing1430 Psychomotor Testing1500 Psychomotor Testing1530 Psychomotor Testing16001700 ------------------- Liquid Diet ----------------------1800

1900 Psychomotor Testing1930 Psychomotor Testing2000 Psychomotor Testing2030 Psychomotor Testing21002200 ------------------ Liquid Diet -------------------------2300 ---------------------- Sleep-------------------------

FIGURE I

Daily activities schedule.

4

Page 8: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

method. The automated technic varied ap- taining thymol and a layer of mineral oil.proximately ± 1.0 mEq./liter from the classic Urine Na+, K+, CI-, phosphate, Ca++, Mg++,method. Calcium and magnesium were deter- and total C0 2 (HCO*-) were carried out by themined by methods developed in-house on the methods described. Urine pH was determinedPerkin-Elmer atomic absorption spectro- with the Astrup AME-1 pH machine; titratablephotometer. acidity (T. A.) was calculated using blood and

urine pH and phosphate by the method de-On selected days hematologic studies were scribed by Pitts (33). Urinary ammonium

performed on oxalated blood by standard tech- (NH,+) was determined by the automatednics. These determinations included micro- method of Logsdon (26). All urine variableshematocrit, hemoglobin, red blood cell count, were reported in milliequivalents excreted perwhite blood cell count and differential, smear 24 hours. In this manner, 24-hour hydrogenfor cell morphology, and s reticulocyte count. ion (11+) excretions could be calculated utilz-As shown in table IV, liver function studies ing the following equation:were also carried out periodically during thestudy. Direct and indirect bilirubin was meas- NH4 + + T. A. - HCO,- = 24-%,. H+ excretion (36).ured by the method of Malloy and Evelyni (28),and SGOT and SGPT enzymes by the Sigma- In addition to the above studios, all sLibjectsFrankel technic (50). Alkaline phosphatase underwent a urine culture before selection todeterminations were carried out by an auto- rule out the possibility of a urinary tract in-mated modification of the King-Armstrong fection with urea-splitting organisms whichmethod (22). Total protein and electrophores's would affect the urinary ammonium excretion.were determined using the Spinco pliper elec- Careful urine sediment examinations were donetrophoresis method. Finally, in the miscel- at selected intervals and daily 24-hour urirelaneous category, blood sugar was determined protein exetioed was approximated utiliziigby the method of Hoffman (18) and blod poteneceidwsapoiae tlzn" ureanitroenby theautomated method of Huffstandard techo'es. Table VI lists the normalurea nitrogen by the automated method of vausfrtilbotryndhetnndSkeggs (51). values for this laboratoryr and the stand-ardSdeviation of determinations carried out. As

To assess arterial acid-base pzrame-ers, the subjects were on a diet containing veryblood was collected from the ear lobes of the little hydroxyprolne, 24-hour urine specimenssubjects. 11e capillary bed was "arterialized' were evaluated for this amino acid to give someby heatinbT the ear lebe to approximately 450 r. insigN into mineral metabolism and parathy--A deep punc turc was then m~ade with a No. 11 roid activity (7, 21, 23). Hydroxyprolines wereBard-Parker blade on a modified handle. Free- determined by an automated modification of

flowing "arteririized" blood was collected Woessner's technic (58).anaerobically in heparinized capillary tubes(60 p1.) containing a small metal filing, sealed Basal cardiopulmonary studieswith clay and mixed with a magnet. Thesesamples were then placed on ice, and pH and Table VII lists the cardiac and respiratoryPco2 determinations were carried out in studies carried out during the test and theduplicate on the Radiometer AME-1 Astrup frequency of determinations. Basal respira-machine (19) within 30 minutes of collection. tory studies were carried out with the subjectsThe efficacy of capillary ear blood equating fasting and recumbent after a 9-hour sleepwith arterial bl'td is well supported in the period. Expiratory minute volume was cal-literature (12, 13, 27), as long as the sample culated from a 4-minute collection i.n a Douglasis from a properly heated capillary bed and is bag with volumes measured in a Tissot spirome-free-flowing. ter. Respiratory rate was sensed by a pressure

Urine studies transducer and recorded on a Sanooi recorder.End tidal air (alveolar air) was collected daily

Urine specimens (24-hour) were collected using the Rahn sampler technic. Samples of

daily in constantly refrigerated bottles con- alveolar air, expired air, and cabin atmosphere

5

Page 9: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

E 0

M4 0 M o t 4 t , - - G

.10 Go o.

000 0

0 k: 'a i ,10 0 U

00

. 0 b

4.44m.E

4jX

'.4to

.0 - U

A. a

0 4.

-bee

m 0 a.

Page 10: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

were collected in syringes lubiicated with sat- man electrodes were positioned on the chest inurated LiCI. Oxygen and carbr.n dioxide frac- such a manner to give a maximum positivetions were determined by the Btckman E-2 QRS deflection and insure adequate cardio-oxygen analyzer and the Liston-Becker-1 or tachometer recordings. Expired air volumes15A infrared carbon dioxide analyzer. From were recorded with a Franz-Mueller gas meter'the above determinations, tidal volume, 02 con- collecting 0.6% of the expired air in a rubbersumption, C0 2 production, and respiratory bag. A Hans-Rudolph low resistant one-wayminute ventilation could be determined. These valve was utilized for gas collection. Expiredare reported in BTPS values. Maximum fractions of 02 and CO2 were measured bybreathing capacity (MBC), vital capacity (VC), methods described earlier. From the aboveand timed vital capacity (TVC) were deter- data, it was possible to calculate -ninute ventila-mined utilizing standard methods. On the days tion, 02 consumption, and CO2 production.that the basal respiratory studies were per-

formedPsychomotor testingfrea 12-lead ECG was also done. Pyhroo etn

Exercise studies All subjects underwent repetitive testing ofseveral types throughout the study. Before

Each subject was exercised twice during the collection of data, subjects were tr-ained foreach control and experimental period. Exercise a time sufficient to insure familiarity with thewas carried out for 1 hour on a Collins bicycle tasks.ergometer with e 100-watt load at 60 r.p.m.Exercise periods were widely separated to pro- An electronically automated series of taskstect again- the' effects of conditioning, as no were carried out three times daily for 30-precondiiu`-•.nig program was feasible. During minute periods (37). Six tasks are involvedthe experimental period, subjects exercised the in this series of measurements. Arithmeticfirst day (acute hypercapnia) and the last day problems presented in two parts necessitate(chronic hypercapnia) in high CO2. Table VIII addition, multiplication, and memory. Pitch,lists the time sequences and number of deter- roll, and yaw maneuver-, were a simpleminations made including pulse response, kigilance task. Satellite tracking measuredminute ventilation, 02 consumption, and CO2 kInd steadincss and compensatory trackingproduction. The pulse rate was continuously maneuvers. A short-term memory task wasmonitored by a cardiotachometer, which re- included after monitoring and counting flash-ceived its signal from a Sanborn electrocardio- ing lights for 1.minute periods. Another prob-gram and recorded heart rate on a beat-to-beat lem-solving task was utilized in reacior controlbasis from the R-R interval. Miniature Beck- tenting, and finally auditory monitoring was

TABLE VII

Basal cardiopulmonary studies

i Cont. 1 Exp. Cont. 2

____Day_2 _ 4 12 '4, 4

Minute ventilation (') I X I X X X X X

0. consumption (Vo2) X X X X X , XC02 production (Vo) X I X X X X X

Maximum breathing capacity (MBC) X X X X X X

Vital capacity (VC) I X X X X X X

Timed vital capacity (TVC) X X X X X

12-Lead ECG X X X X X X

7

Page 11: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

tested utilizing Morse Code and the proper groups in response to elevated carbon dioxide.letter response. Because of these findings the results will be

reported from the pooled data on the 7 subjects.Repetitive psychologic measurements in-

cluding six tests were carried out daily for Acid-base studies3-minute periods. These tests were so designedthat it was impossible to complete the task in Table EX summarizes the period mean forthe time allotted. They included flexibility of each subject with respect to urinary and bloodclosure (finding 4-letter words in rows of let-ters), aiming (quantitating hand steadiness), acid-base parameters. It should be under-

ters, amin (qanttatig hnd teaines), stood that each figure represents a mean ofvisualization, and number facility utilizing stoodeth at ions represent ameaneofarithmetic addition. Measurements were also five determinations and does not adequately

e areflect day-by-day trends. As noted earlier,made concerning speed of closure (canceling all urinary studies are recorded as milliequiv-letters in a row of letters) and speed of per- ale-s per 24 hours so that daily hydrogen ionception. excretion patterns could be assessed. Inspec-

In addition to the psychomotor Lests de- tion of table XI shows the largest changes in

sribed, other tasks were programmed into the arterial pH occur during the acute exposurecri to carbon dioxide. On the first 2 days ofbicycle exercise aspects of the study. Each

subject rode the b'.cycle for a 1-hour perio exposure the most marked pH reduction wassubjectwice dn ctrobicycl, ex raperimental nfrom 7.40 to 7.5 in subject 2. For all 7 sub-twice during control, experimental, and recovery et ,t e o e al m and c e s n p c tlperiods. For the last 25 minutes of each jects, th. overall mean decrease in pH acutelywas from 7.40 to 7.37. In the recovery period,bicycle ride, the subjects were given tasks of the hydrogen ion concentration of the arte-

simple vigilance (light on or off) and a more rialized blood returned to normal. More per-complex auditory memory task dealing with tinent daily hydrogen ion changes will be morecon.binations of letter.- and numbers. adequately appraised in tables X and XL With

IV. RESULTS exposure to the elevated carbon dioxide at-mosphere, a moderate increase (approximately

As shown by an analysis of variance (54), 3 to 4 rm. Hg) was seen in the arterializedthere was little difference between the two capillary Pco2'& - Alveolar gas samples collect-

TABLE VIII

1-Hour exercise pro!ocol

Time (mini.) 1-Min, pulse Minute ventilation (Va) 02 Consumption (Vo2)1 C0 2 production (VC0 2) PsychOMOtor

Resting X X X X

20O

25 X30is X X X X

40

50

55 X X X I60 X

8

Page 12: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

0lg ca040 t- 0a t- 60

___ __ w. 004 ws

_ _ _ _ _ _ _ Lq C CC?0

1,6; w404 0 Co 0 0__ _ __

*a 04 ho to w4 co w0 00 0 0 04 CoC

to &0 LO- w howW

4m ca 0

C% C0* IV C4%q .4! aq ..4

~ o CACAC4 ol ol olCo

EWx- M 04 C-3 Lg* C3 m

cc 'oc4'

IV 00 to -V0Go0V

S. 0000 c 4 hWo ca10 jmj ~ .0 . ~

.4. 0C C-C

V . - e- Goto0 o04040404

03

C4-

:RZ .4 CQ CO V .so C C

000 0- 4 4

Page 13: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

t*0q 0ll aq:, Cý cIoq qo04;0 .4-4. w60 adg .oo 4 WW0

t-04 lilt 40 %

t-W t- t4 - a* c t .4 ob W

.600 WWW '01 ,1t- ad00 t- 0 soW0 40

~) 0 W W ~ o q.ooo o lo~ o b w q~

ttzV-40 olo coON.4 o co 4

.4 0 6 tt- t- b: 4' 000 10006 cio;0 4 t.4 04 co6

t- W @400 000 40.4. 460 00 C4 .4. 1040

* 4z cbG v % 0 w 0

0 0 0 t- 4e t6 0 t t-cc0 oocq we-e aqqR

oo 3 4 10 t4-loo qv 0 @ta0 0 0.

WW 46 4 0 0 ,0 .0W t- CD

C- o*06 C004 0 404 Do 0 004 ~40 to

.4 t0-t-tqw ~ ~ ~ ~ 0 000 tv00 40.0. S I 4!

046004 e4:0 Woo0 L.4 10 WD .

04 CO Vt-os

*q C! 06 0 e 14'0a 0!1 0O0 000 t-6 000P410 t tt. ad04.4 . 4 0 49WW co *2 C c 040l * v04Io w

coW onW 0440 CA00 @0 0 e.I soto

00 00Go 0 W600 CIA0 C%4 0 0 0 wo -Wo 0 co

M6a6b060 W10 P049 b.O 0046 .40

0220 w20 4~O* 000W U

04 I I Il 0~ II *0..4 .4.4 1060

TI +1044 a100

Page 14: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

IS

ed during the study confirmed these observa- To represent more fu!ly day-by-day trends,tions. A small but definite increase was seen pertinent acid-base parameters are reccrded inin serum total C0 2 (HCO3-) with the exposure table X as daily means for flight I and flight II.to the experimental atmoshere. The mean Note that the increase in Paco 2 is quite promptincrease over the experimental period was on the first day as is the reduction in arterial1.5 mEq./liter. With the mild increase in total (capillary) pH. The alveolar Pco 2 remains fair-C0 2, a!. expected decrease was seen in the ly constant through the experimental period,serum chloride of approximately 3 mEq./liter. while small increases are noted in serum totalThe mild reduction in serum chloride was not C02. Commensurate with the increases inmarked enough to determine a definite as- serum total CO2, arterial pH's returned to nearsociated chloruresis. control levels by the fifth day in elevated

carbon dioxide. Table XI illustrates individualAs shown in table IX, the two main renal day-by-day changes in arterial pH. Again,

acidifying parameters (NH4 + and T. A.) were note the prompt but small reduction in arterialunchanged from the first conLrol period pH on day 1 of the experimental period withthrough the experimental period. Mean 24- a gradual return to near control values by thehour NH,+ excretion during control and ex- fifth day in high carbon dioxide. It is note-perimental periods was 21.4 mEq./24 hours and worthy that at no time did the arterial pH20.5 mEq./24 hours, while titratable acidity deviate outside the accepted normal range.excretion was stable at 45.5 and 41.6 mRq./24hours, respectively. As expected, small in- Figure 2 graphically portrays the promptcreases in urinary bierrbonate were noted in rise in Pco2 and fall in arterial pH. The initiRlboth experimental and recovery periods. No reduction in arte.ial pH is gradually returnedsignificant chan•es were noted in 24-hour to near control values by the fifth day as serumhydrogen ion excretion from control to experi- bicarbonate stores increase.mental periods. A definitely significant changewas noted in the recovery period with a reduc- Table XII lists the period means (five de-tion in hydrogen ion excretion. This overall terminations) of urine and serum electrolyteschange was secondary to decreased NH4+ and for each subject during the control and ex-T. A. excretions and an increase in bicarbonate perimental periods. No significant changesin the urine. are noted ini any of the serum parameters in-

TABLE XI

Daily arterial pH determirta•mnsI..

Subject j Cont. 1 Exp. Ii Cont. 2

No. 3 5 1 j 3 4

1 7.39 7.40 7.37 7.37 7.36 7.39 7.38 1 7.42 7.41 7.382 7.39 7.40 7.35 7.37 7.38 7.39 7.39 7.39 7.39' 7.40

3 742 7.38 7.37 7.35 7.37 7.40 1 7.39 7.42 7.40 7.40

4 7.37 7.41 7.37 7.36 7.36 7.36 I 7.38 7.40 7.41

, 7.42 7.40 7.37 7.39 7.38 7.37 '7.38 7.38 7.40 7.41

6 7.37 I 7.39 7.37 7.38 7.38 7.38 7.37 !1 7.38 7.40 7.39

7 Ia 7.39 g 7.41 7.39 7.39 i 7.37 378 7.38 7.39 7.40 7.40

Me 7.39 7.40 7.37 7.37 7.37 7.38 7.38 7.39 7.40 7.40

S.D. 1-.02 ±.01 ±.01 ±1.02 ±.01 t .02 .: .01 :.02 __ .02 t .01

S~11

Page 15: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

46 study. Blood sugar, blood urea nitrogen, and44. serum creatinine determinations were all with-

42 in normal limits and did not reveal any develop-40 ing trends.4s

Liver function studies

Pertinent liver function studies were fol-7.42 lowed throughout the experiment at appro-

7A. .4-e- priate intervals. As shown in table XIII, there1 7.. -3, - were no abnormal values recorded with respect.04 "36 to bilirubin and protein metabolism. SGOT,

SGPT. and alkaline phosphatase determinations30o . were also normal and no developing trends20 were noted.

0 C3O - OHematology studies

A* Red blood cell counts, hemoglobin, hemato-Cot Rcrit, and reticulocyte counts are recorded in

table XIV. There is a mild reduction in allFIGUe 2s (subjects with respect to hematology param-

Acid-baa. atudis (gia of? afibecta). eters. This is felt to be secondary to blood lcss

eluding serum Na+, K+, and Ca++, and P. during the study as approximately one unit ofAll values are well within the normal range. blood was taken from each subject over theMost subjects show little variation in elec- 15-day period. Note the significant increasetrolyte excretion patterns throughout the in the reticulocyte count of subject 7, which

TABLE XIIElectrolyte studies (period means)

Subject U n

No I Na (mEq./24 hr.) U (mEq./2 hr.) Ca (mEq./in hr.) PO4 (eEq./2 hr.)Cout. I Exp- cont.. 2Cont. I EX. I, Cont. 2 Cout. 1 Ep. Cont. 2 Cont. II Exp. Cont. 2

1 l 81 24 J 65 53! 32 88g 83 107 74 61 452 89 86 72 82 j 65. 66 67 88 77 78 77 66

3 153 85 82 93 103 S2 95 104 141 60 '65 634 1100 93 89 79 87 77 30 63 85 66 64 685 92 110 67 108 120 103 87 120 160 88 92' 806 !1 113 72 90 98 85 124 165 162 74 78 707 7 60 2 S3 103! 81 131 123 92 178 ~60 4

Mean 8 8 3 8 78 90 107I 117 74 71 61

P!aszaSubject . Na (mEq./Iiter) I K (mEq./liter) Ca (mEq./liter) ! JO (mEq.Aiter)

Cont. I Exp. Cont. 2 iCont. 1 Exp. Coant 2 Cont..I Rp ' Cont. 2 Cont. i Exp. Cont. 2

1 13 140 138 4.8 4.7 5.0 10.4 10.1 10.6 3.9 4.0 4.12 i 136 139 139 5.2 5.0 5.0 10.1 10.1 10.0 4.2 4.4 4.33 :137 139. 137 5.0 4.9 4.8 102 10.0 10.0 3.3 3.3 3.44 :1135 135 133 4.7 4.9 4.3 10.8 9.9 10.1 3.8 4.2 4.65 139 141 135 4.A 4.8 4.6 10.6 10.4 10.4 3.7 3.8 4.16 140 i139 137 5.0 4.9 4.7 9.9 10.0 10.1 3.8 3.8 4.07 140 140 137 4.9 4.8 4.7 10.3 10.2 10.1 3.5 4.3 4.0

Mean , 138 139 137 4.9 4.' 4.7 10.3 10.1 102 3.7 4.0 4.1

12

Page 16: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

q.4 r: : .9n.9. 9 R

aq CO t,: q 9 it'. t 0 h

-t90. . 1 10 'T -It- 0 0 s

t-~~t t1t0t 6W

b Z t t- t t-L- 0 M t %6 _-.

10.9 eq 00. 00 CO * M OD

t- t V C Go vi C C'aM or *. co

: 2 2t t::b : jz toO to a80 tZ t: - it: t 4 .9 t- t40 cato

O4 to t- t- t- t t- Mo1 . 0 0 1 .

d0 o o ca 0 e 0 ,t

0: vo 0. .4 C> 10 t- t- Q 4 t

to ~ t- oto o0 W.4.4g.4 ' 0 C

02 04

,-.~~~C 10 CD4t O .. 490 t

-A t.. . . . . . . . . . . ..00

0 ~ t- .4 0 t t cc1 t- .9 0 0~ 4=$~~~C m4 W 4 C ( 0 t O ao . C-3

w. . .w t-4D.C

ooI .i *i 0!.4 4.

13

Page 17: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

was out of proportion to the blood loss. This ual oxygen uptake and carbon dioxide produc-was felt to be compatible with a chronic tion studies indicate a change in the R (4 co2 /

hemoly tic process. Careful re-evaluation of V02 ) value relationships largely secondary toblood smears and repeat physical examination a decrease in carbon dioxide production. Asindicated spherocytes on the peripheral blood the subjetts were not trained in breathingsmear and a barely palpable spleen dip. Con- technics, these figures are questionable andsultation with the Hematology Section of Wil- bear further investigation., As expected, thereford Hall USAF Hospital confirmed the is a mild but definite increase in the restingdiagnosis of a chronic hemolytic process sec- minute ventilation of approximately 2.1; liters/ondary to congenital apherocytic hemolytic min.anemia. With the exception of subje-t 7, allblood smears, white blood cell counts, and dif- The table of pulmonary ftnction studies isferential counts were normal during control and self-explanatory. Most valurA are quite normalexperimental phases. with no apparent trends brought out by the

increased carbon dioxide other than mild in-creases in calculated tidrl volume. Again, somevalues of tidal volume (subjects 4 and 7) are

Respiratory studies difficult to interpret and probably secondaryto not having subjects adequately trained in

Tables XV and XVI include studies of using respiratory equipment. There does notoxygen uptake (Vo6), carbon dioxide produc- appear to be any change in maximum breathingtion (Vco2), minute ventilation (VE), and capacity, tidal capacity, and timed vitalvarious pulmonary function studies. Individ- capacity.

TABLE XIV

Hematology studies

Red blood cell count (106/lmL. r Hemoglobin (gsn %)Subject Cont. 1 T Cont. 2 Cont. I Cont. 2

No. Exp. 11 --- Exp.A B! A B IA B _ _ A [ B

1 5.27 530 5.13 5.07 14.9 15.1 14.6 - 13.5

2 5.09 4.54 5.42 - 4.75 14.3 44.5 115.1 - 14.2

3 5.33 I 5.22 15.09 - 4.69 15.4 15.1 15.2 - 14.6

4 4.86 5.07 4.41 3.45 5.22 14.1 14.5 15.2 14.2 14.2

5 4.12 4.85 4.34 5.22 4.18 114.6 14.3 13.8 14.1 13.1

6 5.02 4.30 4.53 4.73 4.86 1 14.8 13.9 15.0 13.9 14.2

7 4.71 4.86 4.88 4.A9 3.72 14.7 12.7 13.9 12.6 13.0

Hematocrit (%) Reticulocyte count (%)Subject Cont. 1 Cont. 2 Cont. I 1 Coat. 2

No. ] B Exp. AI Exp. A A

1 43 46 a s-- 3 0.5 0.3 ! 0.5 - 0.5

2 43 47 44 - 40 0.7 0.6 , .4 _ .04

3 481 49 44 - 45110.5 0.4 0.4A 0.6

4 411 44 44 43 41 1.4 0.8 0.9 0.7 1.7

5 41 43 44 45 42 0.8 0.8 0.5 1.2 0.8

6 1441 40 46 144 41111.010.7 1 -2 1.3 1.77 42 38_3 40_ U8 U__ 1.3 2.0 4.5 5 I9 5.8

14

Page 18: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

Exercise studies psychomotor parameters were tested statis-tically by an analysis of variance. A statistical

Exercise data were collected on 6 of the analysis was carried out on all 7 subjects (in-7 subjects during this study. Data from sub- cluding subject 4 who was actually workingject 4 were deleted. This subject was of quite under a maximum workload). A review of allsmall stature (5 ft. 4 in.; 129 lb.) and had psychomotor and psychologic studies failed togreat difficulty riding the bike as the seat reveal any significant changes or trends whencould not be adjusted tc a low enough level compared to control states. From the fore-for him. As a result of this, every bike ride going, it is concluded that the ambient 3% CO2was a maximum effort for him as he lost all atmosphere did not reveal any detectable per-mechanical advantage. After a short time formance changes in the variables measured.interval on the bike, it was apparent that amaximum effort was involved as heart rates Subjectively, the men felt the atmospherewere 180 beats/min. or above and minute was quite tolerable and in no way interferedventilation was extraordinarily high. with reading, working, or the usual daily ac-

tivities. This is supported by a study of theWith the exception of subject 4, all :subjects daily diaries which they kept. The only

were able to tolerate the 1-hour bike ride quite d symptoms which were related to the atmos-

we!l. Subjectively, all felt well at the end of phere wer c mer ate f ontheadahs,

the exerrise period and even suggested that if phere were mild-to-moderate frontal headaches,

necessary, they could go for a longer period throbbing in nature but not severe enough to

of time. interfere with normal activities. These head-aches occurred in 4 of the 7 subjects and were

Table XVII lists means for all 6 subjects during the first 2 days of CO2 exposure. Threeduring the exercise studies. Measurements of the subjects felt that the headache waslisted include minute ventilation, oxygen up- prominent enough so that an analgesic wastake (Vo2 ), and carbon dioxide production requested. A 32-mg. capsule of dextro-(tca ). Note the increase of 5 to 6 liters/mion propoxyphene adequately relieved distress. A

in resting minute ventilation with almost no general physical examination during the periodchange in 40o2 and Vo.. With the onset of of headaches failed to reveal any abnormalities.exercise a rather marked increase in minute Results from a neurologic examination andventilation of 20 to 25 liters/mi. from control funduscopy were normal. No recurrence ofstates is accompanied by a mild but definite headache was noted after the first 2 days ofincrease in com.d exposure to the experimental atmosphere.There were no complaints of headaches during

Table XVIII outlines the exercise pulse re- the recovery period.sponse in beats per minute. Again, there islittle change in the resting pulse rate from V. DISCUSSIONthe control phase, while a definite increase inpu!qe rate is seen in the experimental period The main points brought out by this studyduring exercise. Generally, the pulse rates in relate to the relatively mild challenge presentedthe last 5-day recovery period are all higher by an atmosphere with an ambient Pco_1 ofthan in the first control period. Finally, a 21 mm. Hg (3%). This is particularly truesteady, moderate workload is mirrored by the when reviewing the mild physiologic changesfact that the pulses remain reiatively stable occurring in acid-base metabolism. As shownafter approximately 15 minutes of exercise. in figure 2, an increase in Paco., of only 3 toThe last 30 minutes of e:aercise were accom- 4 mm. lIg was achieved. Such a small changepanied by psychomotor testing. was accompanied by a minimal reduction inPsychomotor testing the arterial pit of the blood from a control

value of 7.40 down to 7.37, a figure well withinThe Neptune psychomotor testing, repetitive the accepted normal range. As expected and

psychologic measurements, and exercise shown in other studies (2, 49). an initial in-

15

Page 19: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

I.I

TABLE XV

Subject Ao Basal respirat

Sujet Basal 0.cnupin(litersq/mfn., BTPS) _____2prdutin______4LlBTS

No. Cont. I Exp. Cont. 2 Cot ICA B A B A TB A B A B A 1 R

1 .358 SU .8 77 UO A01 .572 .334 .350 .249 .208 M5 .8532 .243 .288 .311 .300 .309 .586 .180 1.274 M2 -048 M7 A473 .314 .381 .407 .291 .281 .236 .281 .262 .234 . 209 94 .693 .487 .533 W2 .441 I .438 .589 .468 .890 .461 .527 .8915 .767 .582 .231 .314 .6A2 .552 .502 .484 .164 .241 .490 .481

a .517 .319 .294 .320 .226 .395 .397 !.295 .240 .W52 .2W1 .370.524 .410 .362 AU .429 .579 .387 .372 .265 .337 M .454

Subject P.Q (rc% 2/_0,) Minute ventilation (literu/min., BTPS)Subject__ AI BA B

NO. Cont. I Exp. Cont.•2 Cont. I Exp. Cot. 2A F1e A B A B A ,B A IB A 'B •

1 .93 J9 .66 .65 (.59 .62 11.1 10.1 11.1 9.3 7.6 10.52 .76 .95 .73 .83 .83 1.76 5.8 8.1 10.1 10.3 7.7 7.43 .75 .85 . .81 ,.74 .75 6.8 7.1 11.0 9.3 6.1 8.54 .85 .96 .73 .87 1.19 .89 14.8 12.5 17.4 18.8 11.2 9.55 .65 .83 .71 .77 .74 .87 13.4 12.1 7.1 11.4 10.1 12.56 .77 .92 .82 .79 1.16 .94 10.2 7.4 9.8 10.0 6.7 &7"7 .74 .91 .7± .74 M .78 8.6 8.2 8.9 11.3 9.5 10.3

TABLE XVI

Pulmonary function studies

Calculated tidal volume (liters) Maximum breathing capacity (litere/min., BTPS)Subject I ___I

No. Cont. I Exp. Cont. 2 Cont. 1 Exp. I Cont. 2A4 B.AS'A B A 1jAB _A B

1 M54 U61 .717 NO .629 1.760 181.0 174A4 179 .0 17 6 .2T 171.9 176.3.453 .611 .523 .683 .540 .836 170.6 187.6 183.7 180.0 U172.6 17.0

3 AS5 .517 72 '.42A .613 185.1 158.0 175.4 166.5 135.6 130.44 1.033 .820 LM 1.298 iL37 .867 173.2 169.5 167.1 163.5 166.6 155.95 .891 1.009 .463 *738 .729 1.018 182.3 161.3 161.4 164.0 163.3 `164.9

6 .796 .534 .638 .798 1.578 .656 152.9 132.8 172.7 169.3 165.2 127.3

5 .5 I 1.363 1416 I 173.6 186.8 180.8 181.6 182.1 189.5

Vital capacity (litere, BTPS) 1-Sec. vital capacity (% .of total) __

Subject Cont.1 I Exp. - Cont. 2 Cont. I Exp. Cont..No. I I .. . - : I !----_-_ B

S1 514775 6.094 6.752 5.631 5.362 5 .800 85 84 85 69 73 802 5.067 ,5.503 5453 5.444 5.308 b.489 ,89 .90 i 89 i 90 92 90

3 5.860 5.720 5.849 5.764 5.330 5.819 87 86 89 88 88 894 '4.701 4.861 4.840 4.840 4.637 4.729 1 87 - '90 92 90 92

5 5.398 5.295 5.752 5.691 5.578 5.530 86 74 85 89 89 866 6.246I 6.068 6.282 6.186 6.048 6.104 V 86 85 8 9 87

7 I 6.519 6.671 6.744 6.851 6.541 6.691 (. 71 75 74 73 74 74

16

I

Page 20: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

crease of approximately 1 mEq./liter in total surprising as a bicarbonate diuresis and sub-CO2 (HCO3-) was seen acutely. Although the sequent increase in urine pH are seen in theincreased acid load, brought on by the elevation first days of the recovery period. It has beenof ambient car'sOn dioxide was minimal, there show i. by other investigators (32) that an in-is still some compensation from the renal --on- creaae in urine pH will definitely decrease theservation of bicarbonate which is controlled by excretion of ammonium and titratable aciditychanges in the Pco2 (35). By the fifth ex- owing to distal tibular changes. The bicar-perimental day, the serum total CO2 (HCO 3-) bonate diuresis was expected upon removalhad increased approximately 2 mEq./liter and from the carbon dioxide atmosphere with re-the arterial pH had returned to near control duction in arterial Pco2 as the kidneyslevels, thus indicating partial acid-base adapta- "dumped" the excessive bicarbonate buf-tion to this environment. fers (32).

Chronic studies carried out by Schwartz Studies by Schaefer et al. (39, 46) andet al. (49) and Sullivan and Dorman (55) in Gtanmeyer et al. (53) in man at 1.5% CO2 andanimals have shown a definite increase in animals at 15% CO.- have raised the questionnet hydrogen ion excretion under high ambient 3f abnormalities of calcium metabolism aadcarbon diox-de levels (7% and 10%). With parathyroid function. As our study was toLthe mild stimulus of this 3% experimental short to carry out a calcium balance, we electedatmosphere, very little was seen with respect instead to investigate urinary hydroxyprnlineto resl changes. It is apparent that no signif- excretion. This amino acid is almost exclusive-icant change (or. more appropriately, increase) ly tied up in collagen tissue and bone and iswas seen in the excretion of urinary NH#+, believed to be a good indicator of parathyroidtitratable acidity, and net hydrogen ion ex- activity (7, 21). Past investigators have showncretion (INH4+ + T. A. - HCO3 -). A marked definite hydroxyproline abnormalities withand statistically significant reduction of NH 4+, parathormone injection, hyperparathyroidism,T. A., and net hydrogen ion excretion is seen calcium infusion, and other states (17. 21,in the followup control period. This is not 23, 30).

TABLE XVII

1-Efour exercise-respiratory studies (period means of 6 subjects)

Cont. I Exp. Cont. 2

A B A B A B

Vn (liters/min., STPD)

Resting 14.9 13.5 19.1 17.6 12.0 10.6

15-20 min. 1 41.5 41.6 66.7 62.7 40.4 38.2

35-40 mrin. 41.7 43.3 67.4 1 65.0 40.0 38.3

5%L55 min. 40.7 43.2 69.6 64.4 39.8 38.9

VO, ,liters/min., STPD) iResting 0.312 0.343 0.353 0.333 L0.313 0.340

15-20 min. 1.364 1.491 1.597 1.576 , 1.304 1.394

35-40 rain. 1.383 1.%95 1.6471 1.5381 1,317 1.417

50-55 min. 1390 1.432 1.697 1.640 1-250 1.352

VCO. (liters/min., STPD)

Resting 0.347 0.353 0.320 0.262 0.297 0.290

15-20 min. 1.480 1.390 1.377 1.259 1.323 1.23 1

35-40 min. 1.367 1.398 1.290 1.2G0 1.263 1.180

50-55 mill. 1.'P•3 1.393 1.365 1178 1 2:3 1.215

17

Page 21: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

TABLE XVIII secondary to the fact that the subjects were

not adequately trained in the use of respiratory

1-Hour exercis,.-;)u.!se response (beats/main.) equipment. One study carried out by Schaefer(period means of 6 subjects) and co-workers (since reported in many places

from 1949 until 1965) does allude to changes

Cont. 1 Exp. Cnt. 2 ini the RQ in high carbon dioxide (40-45). Cur-

A B A B A B rently, more sophisticated studies are being- - -.....-- --r---- -It3- planned to an.;wer this question. The mild

Resting 65 76 73 68 69 increases in resting minute ventilation are to4-5 rin. 114 119 125 132 133 127 be expected and agree with other studies done

14-15 min. 128 130 135 144 144 139 at similar levels (1, 10, 15, 48). Since only24-25 min. 13.5 129 145 152 149 145 two resting minute ventilations wvre deter-34-35 min. ; 132 126 142 151 144 138 mined during the experimental phase, no trends44-45 min. 137 128 144 148 147 143 were noted. The tidal volume studies were49-50 min. 142 135 142 147 148 143 calculated indirectly from minute ventilation59.60 mi.143 •137 ,141 ,148 ,147, 1 and mean respiratory rates and are only ap-

proximations. Large deviations are felt to besecondary to a lack of pulmonary training be-

o4subectsfailed tosho w u ar y chyarox onges dh cause the deviations occur both in experimentalon 4 subjects failed to show any changes which and control phases.

could be attributed to the atmosphere. Some

increases seen in peptides were felt to beseconda.-v to a "deconditioning" phenomenon The significance of the exercise studies inclosely akin to bed rest studies (24, 29), as the this environment is obvious as 6 men were ablesubjects were quite confined and exercised only to carry out moderate workloads for 1 hourduring the six sessions. In addition to relative- without stopping. As noted earlier, none ofly normal hydroxyproline studies, no metabolic them felt it was particularly difficult otherchanges with relation to calcium and rhos- than the increased ventilation they experienced.pherus were seen in urine and serum. Un- Although a low resistance valve w&- used forpublished data from this laboratory have failed gas sampling, it was apparent that it madeto denote any calcium, phosphorus, or hydroxy- breathirng more difficult, and leaks around theproline changes at 4% CO.. for a 5-day mouthpiece cannot be ruled out. As shown inexposure. The whole problem of calci'•-m- table XIV, a small increase in minute 'ventila-phosphorus metabolism, however, has yet to be tion (VE) was noted during the resting stateanswered when considering man and chronic in 'he experimenfal phase with no significanthypercapnia. It will remain for this question change in oxygen consumption. This increaseto be answered in the future with continuing in ventilation was quite marked with the onsetstudies at higher carbon dioxide levels. A of exercise (20 to 25 liters/min.) and probablydefinitive answer could be obtained with a explains the mild but definite increase in

study long enough to incorporate calcium oxygen consumption secondary to the increasedbalance experiments. work of breathing. Carbon dioxide pro-

duction remained within control values. ThisBasal respiratory studies failed to show any rather murked increase in ventilation with

decrease or increase in oxygen consumption moderate exerci's was also seen in Froeb's(Vo;) during exIxsure to the carbon dioxide exercise studiee (10) at ambient levels of 1.5%o mosphere. A rmean of two determinations and 3.4% CO 2. A similar increase in 0. con-on each subject during the control phase of sumption was also noted and thought to bethe experime.,t revealed the RQ was 0.85 secondary to the increased work of breathing.(table XI). This dropped significantly d-ring Although a minimal decrease in ventilation andthe experimental phase of the study. Foilow- oxygen consumption was seen during exerciseup control RQ's returned to 0 85. The reason on the fifth day of carbon dioxide exposure,for this change is still unclear and is possibly no subjective changes were noted by the men.

18

Page 22: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

tThey did not feel that the exercise %as more changes in performance in submarine crew

or less difficult when compared with the acute members during World War 1I. Althoughstudy. definite changes were seen, it is difficult to

attribute them to carbon dioxide alone as noTable XV shows definite increases in pulse information was provided concerning contami-

response during the experimental phase, and nants (carbon monoxide, methane, etc.) knownthese persisted during tLe followup control to build up in closed systems.period. The explanation for this is twofold.First, exercise in the carbon dioxide environ- A statistical analysis of psychomotor testsinert would tend to increase pulse response performed during the exerc:se studies failed to

with the increased vw-ntilsition and work of show any changes from control to experimental

breathing. Second, the factor of decondition- conditions. It should be remembered that the

ing was also present as these previously vigor- data from subject 4 (maximum effort on bike)

ous, active young men who had just completed were also included in the analysis.

basic training were suddenly confined to a Finally, a brief discussion concerning thesmall area with little exercise except for the mild frontal headaches is in order. Carbonprogrammed 6 hours. This obviously was not dioxide is a known cerebrovascular dilator (20).enough to keep good muscle tone, and they Studies by Patterson et al. (31) have noteddeveloped a hypodynamic state. This condition increases of 10% or more in cerebral bloodis well described in simulator studies in several flow, with ambient carbon dioxide levels be-communications by Lamb et al. (24, 29) from tween 3% and 42. These increases, togetherSthe USAF School of Aerospace Medicine. ten3cad4 hs nraetgtetAwith secondary changes in spinal fluid pres-

sure, probably contribute to headaches andThe psychomotor phases of the experiment make them of a vascular nature. Further

were carried out a large number of times and studies concerning cerebrovascular blood flowin great detail. Repetitive psychologic testing in chronic hypercapnia would be of interest,

parametets (tracing of geometric figures, let- but were not indicated here.ter canceling tests, etc.) were programmed intothe study to compare with similar measure- During the 5-day period in carbon dioxide,ments made by other groups. It was felt that the subjects did not feel the environment wasthis was necessary as there is conflicting hostile or particularly uncomfortable. Theyevidence in the literature with respect to were abie to carry out all duties with a maxi-psychorhotor performance and carLon dioxide mum of efficiency and were able to sleepatmospheres, especially at the 3% CO2 level, without difficulty. Outbursts of euphoria, de-Several researchers have failed to note pression, or anxiety were not noted. Complaintssignificant performance changes at ambient from the subjects related mainly to the fre-Pco.:'s ranging from 20 to 38 mm. Hg (3, 5, 57). quent venipunctures and monotonous liquidSchaefer (38, 40), however, reported definite diet.

19

Page 23: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

REFERENCES

1. Alexander, J. K., J. R. West, J. A. Wood, and 12. Gambino, S. R., P. Astrup, R. G. Bateb E j. X.D. W. Richards. Analysis of respiratory re- Campbell, F. P. Chinard, G. G. Nahas, 0.sponse to carbon dioxide inhalation in varying Sigaard-Anderson, -nd R. Winters. Report ofclinical states of hypercapnia, anoxia and acid- the AD HOC Committee on Methodology. Ann.base derangement. J. Clin. Invest. 34:1533 N.Y. Acad. !..i. 133:259 (1966).(1955).

13. Gimbino, S. R. Comparisons of pH in human

2. Brackett, N. C., J. J. Cohen, and W. B. Schwartz. arteri" 1, venous and capillary blood. Amer. J.

Carbon dioxide titration curve of normal man. Clin. Path. 32:298 (1959).

New Eng. J. Med. 272:6 (1965i. 14. Glatte, H., and S. J. Menn. The study of man in

4% CO 2 . (In preparation)3. Consfolazio, W. H., M. B. Fisher, N. Pace. L J.

Pecora. and A. R. Behnke. Effects of man of 15. Hastings, B. K., K. E. Schaefer, G. Nichols, Jr.,high concentrations of carbon dioxide in relation and C. R. Carey. Effects of prolonged exposureto various oxygen pressures during exposures as to elevated levels of carbon dioxide on respira-long as 72 hours. Amer. J. Physiol. 151:479 tion, alveolar carbon dioxide tension and lung(1947). volume. NMRL Report 250 (1954).

4. Cunningham, D. B. B. Lloyd, and C. C. Michel 16. Hawk, P. B., B. L. Oser, and W. H. Summerson.A.Cui-basechanges. in, B..lood, dring .C.Mihe. Practical physiological chemistry, 12th ed. NewAcid-base change, in blood during hyp•.reapnia York: McGraw-Hill Book Company, Inc., 1947.

and hypocapnia in normal man. J. Physiol. Y(London) 161:26P (1962). 17. Henreman, P. H., T. Dull, and T. Lynch. Immo-

bilization and aspirin in Paget's disease. Clin.5. Cutler, R. G., W. G. Robertson, J.. 9. Herlocher, Res. 11:45 (1963).

R. E. McKenzie, F. Ulvedal, J. 3. Hart eaves,and B. E. Welch. Human response to carbon 18. Hoffman, W. S. A rapid photoelectric method fordioxide in the low-pressure, oxygen rich atmos- the determination of glucose in blood and urine.phere. A*rospace Med. 35:317 (1964). J. Biol. Chem. 120:51 (1937).

6. Dripps, R. D., and J. H. Comroe, Jr. The respira- 19. Jorgensen, K, and P. Astrup. Standard bicar-tory and circulatory response of normal man to bonate, its clinical significance and a new methodinhalation of 7.6 and 10.4 ;er cent CO2 with a for its determination. Scand. J. Clin. Lab.

comparison of the maximal ventilation produced Invest. 9:122 (1957).

by severe muscular exercise, inhalation of CO2 20. Kety, S. S., and C. F. Schmidt. The effects ofand maximal voluntary hyperventilation. Amer. altered arterial tensions of carbon dioxide and3. Physiol 149:43 (1947). oxygen on cerebral bi1n, Allow and cerebral

oxygen consumption of =.r.nal young men.7. Dull, T., and P. H. Henneman. Urinary hydroxy- J. Clin. Invest. 27:484 (1948).

proline as an index of collagen turnover in bone.Ney Eng. J. Med. 268:132 (1963). 21. Keiser, H. R., J. R. Gill, A. Sjoerdsma, and F. C.

Bartter. The effect of parathyroid extract on

8. Fawcett, R., and P. P. Newman. Operation Hide- hydroxyproline mptabolism. Clin. Res. 11:41

out (preliminary report). NMRL Report 228 (19).(1953). 22. King, E. J, and A. R. Armstrong. A convenient

method for determining serum and bile phos-9. Fenn, W. 0., H. Pahn, and A. B. Otis. A theo- phatase activity. Canad. Med. Ass. J. 31:376

retical study of the composition of the alveolar (1934).air at altitude. Amer. J. Physiol. 146:637(1946). 23. Klein, L., F. W. Lafferty, 0. H. Pearson, and P. H.

Curtiss. Correlation of urinary hydroxyproline,10. Froeb, H. F. Ventilatory response of SCUBA serum alkaline phosphatase and skeletal calcium

divers to carbon dioxide inhalation. J. AppI. turnover. Metabolism 13:272 (1964).Physiol. 16:8 (1961). 24. Lamb, L E., R. L. Johnson, P. M. Stevens, and

11. Fi.J'e, C. It., and Y. Subbarow. The colorimetric B. E. Welch. Cardiovascular deconditioningjetermination of phosphorus. J. BioL Chem. from space cabin simulator confinement Aero-66:375 (1925). space Med. 35:420 (1964).

20

Page 24: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

r25. Lambertson, C. 3. Carbon dioxide and respiration 38. Schaefer, K. E. Respiration and acid-base balance

in acid-base homeostasis. AneIthesiology 21: during prolonged exposure to 3% carbon dioxide.642 (1960). Pfhieger Arch. Ges. Physiol. 251:689 (1949).

26. Logsdon, E. E. Method for the determination of 39. Schaefer. K. E. Adaptation of men and animalsammonia in biological fluids on the Auto- during prolonged exposure to increased carbonAnalyzer. Ann. N. Y. Acad. Sci. 87:801 (1960). dioxide concentration. Amer. J. Physiol. 163:

747 (1950).27. Maas, A. H. J., and A. N. P. van Heijst. The

accuracy of the micro-deter-nination of the Pco.. 40. 6.•oaefer, K. E. Studies of carbon dioxide tox-of blood from the ear-lobe. Clin. Chim. Acta icity in submarine medicine. NMRL Report6:34 (1961). 181 (1951).

28. Malloy, H T., and K. A. Evelyn. The determina-tion of bilirubin with the photoelectric colorira- 41. Schaefer, K. E. The effect of prolonged exposureeter. J. Biol. Chem. 119:481 (1937). to low carbon dioxide concentrations on flicker

fusion frequency and alpha blocking. NMRL

29. Miller, P. B., R. L. Johnson, and L. E. Lamb. The Report 258 (1954).

effects of four weeks of absolute bed rest oncirculatory functions in man. Aerospace Med. 42. Schaefer, K. E. Respiratory pattern and respira-35:1194 (1964). tory response to CO... J. Appl. Physiol. 13:1

(1958).

30. Ney, R. L, J. R_ Gill, H. R. Keiser, and F. C.Bartter. Regulation of hydroxyproline excre- 43. Schaefer, K. E. Experiences with submarinetion in hyperparathyroidism. J. Clin. Endocr. atmospheres. J. Aviation Med. 30:350 (1959).26:815 (1966).

44. Schaefer, K. E. Respiratory adaptation to chronic31. Patterson, 3. L., A. Heymar., L. L. Battey, and hprana n.N .Aa.Si 0:7

R. W. Ferguson. Threshold response of cere- (1963).

bral vessels of man to incrrate in blood carbon

dioxide. J. Clin. Invest. 34:1957 (1955).45. Schaef-.-, K. E., B. J. Hastings. C. R. Carey, and

32. Pitts, R. F. Physiology of the kidney and body G. Nichols. Respiratory acclimatization to

fluids. Chicago: Year Book Medical Publishers, carbon dioxide. J. Appl. Physiol. 18:107 (1963).

Inc., 1963.

46. Schaefer, K. E., G. Nichols, Jr., and C. i&. Carey.33. Pitts, R. F. The renal excretion of acid. Fed. Calcium and phosphorus metabolism in man

Proc. 7:418 (1948). during acclimatization to carbon dioxide.

J. Appl. Physiol. 18:1079 (1963).34. Prockop, D. J., and A. Sjoerdsma. Significance of

urinary hydroxyproline in man. J. Clin. Invest. 47. Schaefer, K. E, G. Nichols, and C. R. Carey.40:843 (1961). Acid-base balance and blood and urine elec'ro-

lytes of man during acclimatization to A).35. Rector, F. C., Jr., D. W. Seldin, A. D. Roberts, Jr., J. Appl. Physiol. 19:48 (1964).

and J. S. Smith. The role of plasma CO 2 ten-sion and carbonic anhydrase activity in ths 48. Schneider, E. C., and D. Trucsdale. Effects onrenal reabsorption of bicarbonate. J. Clin. the circulation and respiration of an increase inInvest. 39:1706 (1960). the carbon dioxide content of blood in man.

Amer. 3. Physiol. 63:155 (•922).36. Relman, A. S. Renal acidosis snd renal excretion

of acid in health and disease. Advances in

internal medicine, vol. XJI. Chicago: Year 49. Schwartz, W. B., N. C. Brackctt, and J. J. Cohen.

Book Medical Publishers, Inc., 1964. The response of extracellular hydrogen ion con-

centration of graded degrees of chronic hyper-

37. Rodgin, D. W., and B. 0. Hartman, The study capnia: The physiologic limits of the defense

of man during a 56-day exposure to an oxygen- of the pit. J. Clin. Invest. 44:291 (1965).

helium atmosphere at 258 mm. Hg total pres-sure. XIII. Behavior factors. Aerospace Med. 50. Sigma-Frankel procedure. Sigma Technical Bul-

37:605 (1966). letin No. 505, pp. 1-10, Jan. 1961.

21

Page 25: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

51. Skegg., L. T. An automated method for coori. 56. Technicon Laboratory, New York. AutoAnalyzermetrr! analysis. Amer. J. Clin. Path. 28:311 method N-20A.(1957)

52. Skeggs, L. T. An automatic method for the 57. White, C. S., J. H. Humm, E. D. Armstrong, anddetermination of carbon dioxide in blood plasma - N. P. V. Lundgren. Human tole-"_nce to acuteAmer. . CJin. Path. 33:181 (1960). exposure to carbon dioxide. J. Aviation Med.

23:439 (1952).

53. Stanmeyer, W. R., C. T. G. King, H. Scofield, and

R. Colby. The effect of prolonged exposure tocarbon dioxide on calcification. In Schaefer, 58. Woessner, J. F., Jr. The determination ofK. E. (ed.). Man's dependence on the earthly hydroxyproline in tissue and protein samplesatmosphere. New York: Macmillan Company, containing small proportions of this imino acid.1962. Arch. Biochem. 93:440 (1961).

54. Steel, R. G. D., and J. H. Torric. Principles andprocedures of statistics. New York: McGraw- 59. Zharov, S. G., Ye. A. Il'in, Ye. A. Kovalenko, I. R.Hill Book Company, Inc., 1961. Kalinichenko, L I. Karpova, N. S. Mikerova,

M. M. Osipova, and Ye. Simonov. Effect on55. Sullivan, W. J., and P. J. Dorman. Renal response man of prolonged exposure to atmospheres with

to chronic respiratory acidosis. J. Clin. Invest high carbon dioxide content. Aviation and34:268 (1955). space medicine (Moscow), pp. 182-185, 1963.

22

Page 26: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

UnclaosifiedSecurity Classification

DOCUMENT CONTROL DATA- R&D(SocnIty Classlfication of title. body of otttrect end tndexng annoteaton must be e*tnad when the ovteall report s. cleassfied)

I ORIGINATING ACTIVIY (Corporaete auhor) 5 REPORT SECURITY CLASSIFICATION

USAF School of Aerospace Medicine UnclassifiedAerospace Medical Division (AFSC) 2b GROUP

Brooks Air Force Base, Texas3 REPORT TITLE

CARBON DIOXIDE TOLERAICE STUJILS

4 DIESCRIPTI% E NOTES (Type of reprt and ilnclusive dates)

1966S. AUTHORFS, Lost name. limt name. Initial)

Glatte, H. A., Jr., Captain, USAF, MCIMotsay, G. J., Captain, USAF, MCWelch, B. E.

6 iEPORT OATE 7j TOT*L NO OF PAGES 7b NO Or iFrs

Aý,,ust 1967 22 59Ila. O.TRACT O0 GRANT NO. 10 ORIG-.ATOR'S acpowT Numacksi

Ilk 'ontract No. T-41829-G y, T "0•.o 7930 S•r4-TR-67-77

c. Ta No- 793002 I6 ________PORTMOMAn_______ _otmaybe

10 A VA ILAIL'TY/LIMITATION NOTICES

This dozument has been approved for public release and sale; itsdistribution is unlimited.

It. SUPPLEMENTARY NOTIFS t2- SPONSORING MILITARY ACTIVITY

USAF School of Aerospace MedicineAerospace Medical Division (AFSC)

_ _ __ Brooks Air Force Base, Texas13 ABSTRACT

'Seven normal volunteers were expnsed to an environment of 21 mm. Hg CO2(3%) for a 5-day experimental period bracketed by two 5-day control periods.Measurements included daily serum and urine electrolytes, blood gas studies,and net acid excretion studies. Also included were detailed investigationsof respiratory physiology, exercise resporse, and psychomotor performance.All subjects tolerated the experimental atmosphere with no undue problems.Arterial and alveolar Pco t's increased 3 to f rmm. Hg with a mild reduction inarterial pH from 7.4O to 1.37. Arterial pH values returned to near controlvalues by the fourth day. No increases were noted in net acid excretion.Exercise was tolerated remarkably well.

DD, I" 434 1473Security Classification

I l~l m • m m~mlm mm~mm• ll9•~

Page 27: CARBON DIOXIDE TOLERANCE STUDIES - DTICtory effect the elevated PcO2 has on respira- determined by the automated method of tory minute volume, the partial pressure of Skeggs (52)

l~ne-1 asqi f ij P _______

SecutitzClassification_______ ______________

14 LINK A LINKS9 LINK CKYWRSROLM WT ROLM WT ROLM WT

Phyiology, rtdesprt yan exercise __

Carbon dioxide studies

INSTRUCTIONS LiL. ORIGINATING ACTIVITY: Enter the name and address imposed by security classification;~ using stafidard statementsof the contractor, subcontractor, grantee. Department of De- such as:lens* activity or other organization (corporate author) isuing (1) "Qualified requesters my obtain copies of thisthe report- report from DDC."*

2.. EPOT SCUNY CASSFICAION Eas? he we? (2) "Foreign avaouincement and dissemination of thisall security classificatlrn of the repo.-t. Indicate whetherreotb Diswauoved1"Restricted Date" is inciudnd. Marking isa to be In accord- eotb D sntatoie.ance with appropriate security regulationa. (3) "U. r. GC'wernment agencies may obtain copies of

2b. GROUP* Automatic downgrading is specified in Do)D i- this report directly from DDC. Other qualified DDCrective 5200. 10 and Asmed Forces Industrial ManuaL Enter users shall reqpest throughthe group number. Also, when applicable, show that optionalmarkings have been used for Groo" 3 and Group 4 as author- (4) --U. S. military! agencies may obtain cogies of thisized. report directly from DDC. Other qualifted oraers

3. REPORT TITLE_' Erder the ceouplaet report tiiie in all shall request throushcapital letters. Titles in all cases should be unclassified.If a meaningful title cannot be selected without classifica-tion. show title classification in all capitals in parenthesis (5) "All distribution of this repo.t is controlled. Qural-immediately following the title. ified DDC users ahall request through

4. DESCRIPTIVE NOTES: If pptopriate, enter the type of .______________I__reprt. e~g.. interim, Prowess. summary. annual. or final. If the report has bee furnished te the Office ef TechnicalGive the inclusive dates when a specific reporting period is Services. Depammert of Commerce. for sale to the public, indi-covered, cate this fact sad enter the price, if known.S. AITHOR(S).' Eater the name(s) of author(s) as shown on IL SUPPLEMENTARY NOTE& Use foe additoal esplana.-or in the report. Enter last name. first name. middfle initial. tory notes.If m.ilitary. show rank and branch of sevice. The Roes ofthe principal outhor is an absolute mintmum requirement. 12. SPONSORING MILITARY ACT!VITY: Eater the nev2 of

the departwouetal project office or laboratory sponruorinr (par6. REPORT DATE: Enter thi date of the report as day. ing tor) the cessearch and development. Include address.m',nth. year. or month year. If more than one date appearson the report, use datae f publication. 13. AaSTRACT: Enter an abstract giving a brief and factual,

aummazy of the document indicative of the report, even though7&. TOTAL NUMBER OF PAGES: The total page (qount it may also appear elsewhere in the body o. the technical re-shouid follow anormal pagination procedures, L~e.. enter the gort If additiopal %pace is required, 4 continuation sheet emulinumber Of pages containing informnation. be attached.7b. NUMBfER OF REFERENCES: Eater the total number of It is highly desirable that the abstract of classified reporsreferences cited in the report. be unclassified. Each paragraph of the abstract shall entd withan. CONTRACT OR GRANT NUMBER:- if appropriate, enter Sn indication of the military security classification of the in-

the. appItcable number of the contract or greant under which formation in the paragraph, represented as (Ts). (s). (c). or (tI).the report was written. There is no limitation cn the length of the abstract. Hlow.Sb, 11. at Ad. PROJECT NUMBER Enter the appropriate ever, the suggested length is from 150 to 225 words.military departmew. identification. such as Project number,. 4 E OD:Kywrsaetcnclymaigu emsubproject number, system numbers, task number, etc.14KEWOD:eywrsaetcnalymnigutrs

or short Phrases that characterize a report en.d may be used as9s. ORIGINA711R'S REPORT NUMBER(S): Eater the offi- index entries for cotalograg the report. Kay words must becial report number by which the document will be identified selected so that no security classification is required. Identi-and controlled by the originating activity. This num~ber must fiers. such as equipment model designation, trade name, militar7be unique, to this report. Project code name. geographic location, may be used as key9b. OTHER REPORT NUMBER(S)- If the report has bee words but will be followed by an indication of technical con-

assigned any other report numbers (either by the originator text. Teassignment of links. rules. *ad weights is optional.or by the sponsor), elso enter this numberms).10. AVAILABILITY/LIMITATION NOTICES: Enter any lim-itations, on further dissemination of tho report, other than thosel

QWo gsMSSI Unclassified

Seuraity Classification