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THE EFFECTS OF BODYPOSITION, GANGLIONIC BLOCKADEANDNOREPINEPHRINEONTHE PULMONARY

CAPILLARY BED* tBy BENJAMIN M. LEWIS, WILLIAM T. McELROY,t ERNESTJ. HAYFORD-

WELSING§ AND L. CARL SAMBERG

(From the Pulmonary Function Laboratory, Department of Medicine, Wayne State Universityand City of Detroit Receizing Hospital, Detroit, Mich.)

(Submitted for publication February 17, 1960; accepted April 7, 1960)

Roughton and Forster (1) have demonstratedthat the volume of blood in the pulmonary capil-laries (V,) and the true diffusing capacity of thepulmonary membrane (DM), which, presumably,is related to the thickness and area of the pulmo-nary capillary wall, may be calculated from meas-urements of the pulmonary diffusing capacity forcarbon monoxide (DLCO) at several different cap-illary oxygen tensions. Their method makes pos-sible the study in the intact human of a capillarybed which is of great physiological and clinical im-portance. We have previously studied (2) thebehavior of this bed in mild exercise and duringchange in position. In the present study, we haveinfused a ganglionic blocking agent and norepi-nephrine during change of body position and havecorrelated the changes which occurred in V, andDM with available information on the cardiovas-cular effects of these procedures to explore themanner in which the pulmonary capillary bed isregulated.

MATERIALS AND METHODS

Subjects for these studies were young adult male vol-unteers in good health. Physical characteristics of thesesubjects are given in Table I. In each subject, the ten-sion of carbon monoxide in equilibrium with capillaryblood was determined by a rebreathing method (3). Thesubject then lay on a comfortably padded tilt table and

* The material was presented in part at the fall meetingof the American Physiological Society, London, On-tario, Sept. 5, 1958 and at the Midwestern Section of theAmerican Federation for Clinical Research, Chicago, Ill.,Oct. 30, 1958.

t This work was supported by grants from the Na-tional Heart Institute (H2379), the Receiving HospitalResearch Corp., and the Michigan Heart Association.

t This work was performed during an American Physi-ological Society Summer Research Traineeship.

§ This work was performed during tenure of a Fellow-ship with the Michigan Heart Association.

an intravenous infusion of 5 per cent dextrose in waterwas begun and allowed to run slowly. The experimentalprocedure shown in Table II was then carried out.

The infusion solution was then changed to either tri-methapan camphor-sulfonate (Arfonad), a ganglionicblocking agent (5), 1 mg per ml, or norepinephrine(Levophed), 4 /ug per ml. The rate of infusion of tri-methapan was regulated so that the systolic blood pres-sure after one minute in the 450 head-up position wasapproximately 90 mmHg; the rate of infusion of nor-epinephrine was regulated to maintain a systolic bloodpressure of 140 mmHg in the recumbent position. Theexperimental procedure given above was then repeated.In all studies in which trimethapan was used, the infu-sion was discontinued and a final equilibrium Pco wasmeasured. Initial and final measurements of equilibriumPco were used in computing DLco (2). In four of thesesubjects another control determination and study duringthe infusion of norepinephrine were carried out. In twosubj ects in whom norepinephrine was infused first, theinfusion fluid was changed to trimethapan and a thirdset of measurements made under these conditions.

The Po2 of each of the rebreathing bags was meas-ured by a paramagnetic oxygen analyzer.' The recipro-cal of the reaction rate of CO with hemoglobin at thisPo2 (1/6) was taken from the published graphs ofRoughton, Forster and Cander (6) assuming X of 2.5,and the V, and DMin each position were obtained graphi-cally from the plot of 1/e against 1/DLco.

TABLE I

Physical characteristics of subjects

VitalSubject Age Ht Wt capacity

yrs cm kg LA. L. 24 180 73 6.1E. H. 23 183 86 4.0C. L. 31 180 73 2.9D. J. 22 180 76 5.2M. N. 23 175 77 4.6N. Z. 35 171 80 4.4J. L. 23 172 76 3.7K. T. 22 178 64 4.6

1 Model E2,Calif.

Beckman Instruments, Inc., Fullerton,

1345

LEWIS, McELROY, HAYFORD-WELSINGAND SAMBERG

TABLE II

Plan of experiment

Time Position Gas breathed Measurements*

min sec0 0 Recumbent Oxygen2 0 450 Head-up Oxygen3 0 Recumbent Oxygen4 0 Recumbent 0.3% CO, 10% He, DLCO, blood pressure,

89.7% 02t pulse4 30 Recumbent Oxygen6 30 450 Head-up Oxygen7 30 45° Head-up 0.3% CO, 10% He, DoO, blood pressure,

89.7% 02t pulse8 0 Recumbent Roomair

11 0 450 Head-up Roomair12 0 Recumbent Roomair13 0 Recumbent 0.3% CO, 10% He, DLuo, blood pressure,

21% 02, 68.7% N2t pulse13 30 Recumbent Roomair15 30 450 Head-up Roomair16 30 45° Head-up 0.3% CO, 10% He, DLoo, blood pressure,

21% 02, 68.7% N2t pulse17 0 Recumbent Roomair

* DLco was measured by a rebreathing method (4).t Obtained from The Matheson Company, East Rutherford, N. J.

RESULTS

The results obtained are shown in Table III.These data are summarized in Table IV. Ar-rows indicate significant differences when thedata are subjected to variance analysis (7). In

the trimethapan group, studies on D. J. and J. L.are included although norepinephrine was ihfusedbefore trimethapan was given. The changes fol-lowing trimethapan in these subjects are of ap-

proximately the same magnitude and direction as

in those in whom trimethapan infusion immedi-ately followed the control. The direction ofchanges from the recumbent position during thevarious procedures employed is indicated inTable V.

DISCUSSION

Limitations of the methods. We have dis-cussed elsewhere the accuracy of the rebreathingmethod of measuring DLCO used in these studies(4) and of the computation of V, and DM (2).

With regard to the rebreathing method, we con-

cluded that the values obtained by its use are lesssubject to errors due to uneven ratios of diffusingcapacity to alveolar volume or to alveolar ventila-tion than other methods using carbon monoxide.Further, any changes in the volume of the lungduring the procedures used in these studies are

taken account of, since a measurement of the com-bined volume of lung and rebreathing bag is ob-tained simultaneously with a measurement ofDLCo.

With regard to the computation of V, and DM,we felt that the values obtained were approximaterather than exact and that the chief usefulness ofsuch computations lay in detecting changes inthese parameters. The fact that the values of V,and DM that satisfy a given value of DLCO lie ona rectangular hyperbola must be borne in mind inassessing the significance of such changes. Be-cause of this relation, it is possible that a changein DLCO within the limits of experimental errormight cause a striking change in the computedvalues of V, or DM. Standard statistical meth-ods, such as those used in this study, should dis-tinguish such random changes from significantalterations. In addition, we may compare dataon the effects of tilting in the present study withdata we have previously reported (2) on changesin V, and DM in the sitting and recumbent posi-tions using a different method of measuring DLCO(Table VI). The absolute values for DLo andV, differ, especially the latter, but the directionof change is the same. DMincreased in the sittingposition in the single breath studies, but did notchange in the rebreathing data. However, the

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EFFECT OF POSITION AND DRUGSON PULMONARYCAPILLARY BED

TABLE III

Measurements of diffusing capacity, capillary volume and membrane diffusing capacity*

DLcO

Subject Position Drug Po2 100 Po2 600 Vc DM Blood pressure Pulse

ml/mmHg X min

R N 39.6T N 36.5R A 38.8T A 38.6R N 35.8T N 37.5R L 44.5T L 43.8

26.520.423.219.822.619.123.123.5

R N 37.4 24.6T N 34.7 21.2R L 42.4 25.4T L 38.2 23.4

R N 32.0 19.9T N 24.0 15.0R A 30.3 15.3T A 22.0 12.0

R N 39.1T N 37.1R L 48.5T L 36.4R A 35.5T A 30.9



R N 23.6T N 21.0R L 23.0T L 23.0R A 20.3T A 19.6

R NT NR AT AR NT NR LT L

34.834.336.030.834.833.039.234.0

21.719.827.021.718.415.3

18.416.817.515.217.816.418.917.5

15.212.614.111.114.712.215.916.2

14.513.914.815.613.211.2

20.118.419.615.321.117.922.821.8

ml/mmml Hg X mi

211 52125 60153 60107 84175 50107 83137 99151 72

176145182167

mmHg113/67100/73

* 101/64102/74105/61103/74140/81141/82

52 120/8054 118/9264 143/8655 141/87

143 47 130/100120 33

83 62 137/9269 41 80/57

143 64 120/170119 69 112/68159 84 128/85154 55 140/91105 67 100/7187 62 86/74

109 59 118/78112 45 119/88119 45 115/82

95 45 101/90125 44 124/78107 47 124/88135 48 151/99132 42 142/91

11479

11477

13985

128119

35 106/8035 106/8229 100/8028 90/8027 111/7430 107/7532 144/9338 136/85

95 37 110/65104 30 108/83108 33 140/100130 31 140/93100 28 102/72

71 35 70/58

13011112290

144113150158

59 108/6462 102/7757 98/6855 78/6655 107/6558 102/7565 146/8951 142/83

5771677966855666

58595953

A. L.

E. H.

C. L.

D. J.

M.N.

N. Z.

J.IL.

K. T.

7076576871

102

7788

101122

81987679

6062628266644954

7584485984

120

6571638763705150

* The following abbreviations are used: R, recumbent; T, tilted 450; N, glucose infusion; A, trimethapan (Arfonad)infusion; L, norepinephrine (Levophed) infusion; DLCO, diffusing capacity of lungs; po,, approximate alveolar oxygentension; VC, capillary blood volume; DM, membrane diffusing capacity.

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TABLE IV

Summary of results *

DLco

Po2 100 Po2 600 VC Dm

Condition R T R T R T R T

Control 32.1 - 29.1 19.5 16.7 135 110 51 48

Trimethapan 30.2 -f 26.7 17.3 -- 14.3 114 85 50 51

Control 31.5 30.2 19.6 17.2 143 111 47 5312 t 1i / i t 1i

Norepinephrine 36.3 33.0 21.1 19.9 143 144 61-'-49

* Abbreviations are the same as in Table III. Arrows indicate significant differences.

TABLE V

Relation of V, and Dmto hemodynamic changes *

Position Procedure PAP CO PCP PVR TMP VC DM Reference no.

Tilted None 4. 4. 4. t 4 4. 0 (8)Recumbent Trimethapan 4. 4. [4.] [0] 4. 4. 0 (9, 10)Tilted Trimethapan [4.4.] [4.4.] 4.. 4. 0 (I11)Recumbent Exercise t t 0 0 1' t t (2, 12)Recumbent Norepinephrine t 0 t ? t 0 t (13, 14)Tilted Norepinephrine [0] [t] 0 0 Text

* Abbreviations: PAP = pulmonary artery pressure; CO= cardiac output; PCP = pulmonary "capillary" (orwedge) pressure; PVR = pulmonary vascular resistance; TMP= transmural pressure in capillary (deduced, see text);blank = no data; ? = conflicting results. Arrows indicate direction of change from recumbent position, no drugadministered. For other comment see text.

conclusion drawn from the two sets of data isthe same. In each case there is an increase insurface area and/or decrease in diffusion pathper unit of capillary volume. This comparisonstrengthens our confidence in the qualitative va-

lidity of the changes found in these studies.Interpretation of results. Physiological study of

the capillary circulation of the lung has been madedirectly by biomicroscopy and indirectly by thetechniques used in this study. The available dataon the behavior of the pulmonary capillaries usingthe indirect technique are summarized in Table V.

The pulmonary capillary bed may either pas-sively conform to events elsewhere in the cardio-vascular system or possess active vasomotion.That is, the observed changes in this bed may beeither secondary or primary.

The notion of a passive or secondary change inthe pulmonary capillary bed needs some clarifica-tion. For a vessel which contains muscular andfibrous* elements in its wall (as arterioles andvenules), the criteria for such a change have beensuccinctly stated by Burton (15): The size of avessel is governed by the pressure difference be-

TABLE VI

Effects of position; comparison of methods *

DLCO

PO2 100 PO2 600 VC Dm

Method Subj ects R T R T R T R T

Single breath 4 31.6 26.9 15.0 11.5 86 59 77 99Rebreathing 7 32.1 29.1 19.5 16.7 135 110 51 48

* Abbreviations are the same as in Table III. "Single breath" results were previously published (2) and weredone in sitting rather than tilted position.

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tween its lumen and the surrounding tissue (trans-mural pressure) and by the tension in its wall.If the size changes in the same direction as thetransmural pressure, this change may be (but notmust be) passive; if size and transmural pressurechange in opposite directions, active vasomotion isinvolved. Capillaries, however, are simple endo-thelial tubes and on biophysical grounds shouldopen fully if the transmural pressure exceeds acertain value (critical opening pressure); no gra-dations in patency between closed and fully openshould occur (16). The remarkable constancy ofpulmonary capillary diameter seen by biomicros-copy (17) confirms this prediction. To call achange in the pulmonary capillaries passive wemust assume that the critical closing pressures ofthe pulmonary capillaries cover a range of valuesfrom low to high and that these critical closingpressures do not alter during the change in ques-tion. Then, during a rise in transmural pressurethe critical opening pressure of certain capillariespreviously closed should be exceeded and thesecapillaries will open, increasing V, (or vice versaduring a fall of transmural pressure). If theseassumptions are not proved, active vasomotioncannot be excluded. On the other hand, if trans-mural pressure and V, change in opposite direc-tions, the change cannot be explained on a passiveor secondary basis and active vasomotion is in-volved.

Wre are not aware of measurements of pulmo-nary capillary transmural pressure. However, themean capillary transmural pressure must bearsome relation to the pressure in the pulmonaryarterv and the pulmonary veins.

In Table V we have summarized the data avail-able on the changes in the pulmonary circulationduring the procedures we employed and our de-ductions from this data as to changes in the capil-lary transmural pressure. Transmural pressuremust, of course, exceed pulmonary venous pres-sure and, barring venous constriction, these twopressures must change together. Pulmonary "cap-illary" (or wedge) pressure is an acceptable meas-ure of pulmonary venous pressure in man (18),and in Table V we have used it as an index ofchanges in transmural pressure. Pulmonary arterypressure is a less reliable guide to changes intransmural pressure because, although it must al-

ways exceed transmural pressure, the two neednot change together, since the resistance of thepulmonary arterioles is interposed.

In addition to mean pulmonary artery pressureand pulmonary arteriolar resistance, the trans-mural pressure in the capillaries may be affectedby changes in the vertical distance from the cap-illaries to the root of the pulmonary artery duringchanges in position. We believe this last factoris of less importance than the other two since itseffects tend to cancel out. The anterior portionsof the lungs are supplied against gravity in therecumbent position while the superior portions aresimilarly affected in the erect position. The wellknown decrease of oxygen uptake in the upperlobes when the subject is upright (19) has as itscorollary an increase in oxygen uptake in thelower lobes.

Certain comments on Table V should be madehere. Wehave not found measurements of pulmo-nary "capillary" pressure during trimethapan ad-ministration and have used the data of Fowler andassociates (10) for a related drug, tetra-ethylammonium. Fowler (11) does not specify theganglionic blocking agent used in his studies. Thedata on pulmonary vascular resistance during nor-epinephrine administration are conflicting (13,14), but the conclusion that capillary transmuralpressure rises seems warranted, regardless ofchange in pulmonary vascular resistance. Thedata on the effects of norepinephrine infusion dur-ing head-up tilt are scanty. DeFazio, Regan andBinak 2 have found that cardiac output did notchange when a patient was tilted during norepi-nephrine infusion. The secretion of norepineph-rine is a normal response to assuming the uprightposition (20) and deficiency of such secretion hasbeen reported in orthostatic hypotension (21).Presumably, norepinephrine infusion prevents ve-nous pooling and thus maintains cardiac output,pulmonary artery pressure and transmural pres-sure at or above control values. The data whichhave been specificially mentioned above are indi-cated by brackets in Table V.

It will be seen that during tilting, trimethapaninfusion and exercise, transmural pressure and V,change in the same direction. These changes

2 Personal communication.

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might be passive or secondary to the variation intransmural pressure brought about by events else-where in the cardiovascular system. However,during norepinephrine infusion in the recumbentposition in which hemodynamic data suggest thatcapillary transmural pressure increases, V, doesnot change. This is evidence in favor of activevasomotion in the pulmonary capillary bed.

The possible site of such vasomotion is of inter-est. In general, arterioles are joined to venulesby thoroughfare or preferential channels whichhave thin muscular walls and are direct continua-tions of the feeding arteriole. True capillariesarise as lateral branches of these thoroughfarechannels (22). Garcia-Ramos (17) has con-cluded that this arrangement of thoroughfare chan-nels with lateral branches exists in the lungs. Aring of smooth muscle (precapillary sphincter) isknown to exist at the junction of true capillarieswith their thoroughfare channels in other organsand such sphincters are exquisitely sensitive tocirculating vasoconstrictors like norepinephrine(22). If such sphincters existed in the lung, theirconstriction might prevent the increased trans-mural pressure from opening previously closedcapillaries.

It should be reiterated at this point that becausea change in capillary volume could be explainedby a passive conformity of the capillary bed to achange in transmural pressure does not mean thatthis is the mechanism involved. The occurrenceof capillary vasomotion is not excluded in certainof these situations. Thus, if the norepinephrinesecreted during tilting (20) were to constrict theprecapillary sphincters, capillary volume might de-crease independently of changes in transmuralpressure. However, capillary volume goes up onexercise when norepinephrine release also occurs(23) and trimethapan, which should block nor-epinephrine release, causes a more profound dropof capillary volume on tilting, not a less profoundchange as one might predict if one views capillaryvasomotion as the mechanism governing the cap-illary bed. This, of course, assumes that tri-methapan has no action of its own on the precap-illary sphincters as shown in the rat mesentery(24).

Thus, from the limited evidence available, thechanges in capillary volume which occur on tilting,

during exercise and during trimethapan infusioncan be more readily explained as passive responsesof the capillary bed to events elsewhere in thecardiovascular system, which vary transmural pres-sure, than as active vasomotion of this bed. How-ever, the fact that capillary volume does not in-crease during norepinephrine infusion suggeststhat under certain circumstances active vasomotiondoes occur in the pulmonary capillary bed. It ispossible that both secondary and primary effectson the capillary bed occur in most situations, butmore subtle experiments involving perfusion andquantitative biomicroscopy would be necessary todetect this interaction.

Interpretation of the changes in DM in thesestudies is more complex than that of the changesin V,. DMpresumably is a measure of the surfacearea of the capillaries in contact with the alveoliand of the distance that gas must travel fromalveolus to capillary. Either or both of theseparameters may change.

According to the Starling hypothesis, in a"solid" organ capillary transmural pressure, theosmotic pressure of the blood, and tissue pressureare in equilibrium. If transmural pressure rises,fluid passes from the capillary until tissue pressureincreases to restore equilibrium. The process isreversed if transmural pressure falls. It is notknown if significant tissue pressure can developin this way between the alveolar and capillarywalls in a "spongy" organ like the lung or if fluidpassing from the capillary remains within this wall,thickening it. If this latter process does occur, afall in transmural pressure would cause fluid toenter the capillary and decrease the distance fordiffusion. This is a possible explanation of thefinding that DM did not change during tilting ortrimethapan infusion, which decrease transmuralpressure. During exercise both DM and trans-mural pressure increase. V, also increases, how-ever, indicating that more capillaries are open withgreater surface area. The increase in DMduringnorepinephrine infusion remains unexplained.

Measurement of changes in lung tissue volume(25) concurrently with D-I\ might place interpre-tations of DMon a sounder footing. Thus, if lungtissue volume were to fall on tilting, although DMdid not change, there might be some support forthe speculation advanced above that this is due to

1350


passage of fluid from the alveolar capillary spaceinto the capillary.

SUMMARY

1. The pulmonary capillary blood volume (V0)and the diffusing capacity of the pulmonary mem-brane (DM) were calculated from measurementsof diffusing capacity of the lungs for carbon mon-oxide (Drco) in normal subjects in the recumbentand 450 head-up tilted positions, during a controlperiod and during the infusion of trimethapan(Arfonad) and norepinephrine (Levophed).

2. V, fell during head-up tilting. The infusionof trimethapan in the recumbent position also de-creased V, and accentuated its decrease during thehead-up tilt. DMdid not change significantly dur-ing these procedures.

3. Norepinephrine did not change V, in therecumbent position, but led to an increase in DM.The decrease in V, on tilting was abolished bynorepinephrine.

4. V, changed in the same direction as did thecapillary transmural pressure deduced from avail-able hemodynamic data during tilting, trimethapaninfusion, and exercise. This could be due to pas-sive conformity of the capillary bed to changes intransmural pressure. Active vasomotion, however,cannot be excluded. V, did not change, althoughtransmural pressure probably was increased duringnorepinephrine infusion in the recumbent position.This is best explained by active vasomotion in thepulmonary capillaries.

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portance of diffusion and chemical reaction ratesin determining rate of exchange of gases in thehuman lung, with special reference to true diffus-ing capacity of pulmonary membrane and volumeof blood in the lung capillaries. J. appl. Physiol.1957, 11, 290.

2. Lewis, B. M., Lin, T.-H., Noe, F. E., and Komisaruk,R. The measurement of pulmonary capillary bloodvolume and pulmonary membrane diffusing ca-pacity in normal subjects; the effects of exerciseand position. J. clin. Invest. 1958, 37, 1061.

3. Sj6strand, T. A method for the determination ofcarboxy haemoglobin concentrations by analysisof the alveolar air. Acta physiol. scand. 1948, 16,201.

4. Lewis, B. M., Lin, T.-H., Noe, F. E., and Hayford-Welsing, E. J. The measurement of pulmonary

diffusing capacity for carbon monoxide by a re-breathing method. J. dlin. Invest. 1959, 38, 2073.

5. Randall, L. O., Peterson, W. G., and Lehmann, G.The ganglionic blocking action of thiophaniumderivatives. J. Pharmacol. exp. Ther. 1949, 97,48.

6. Roughton, F. J. W., Forster, R. E., and Cander, L.Rate at which carbon monoxide replaces oxygenfrom combination with human hemoglobin in solu-tion and in the red cell. J. appl. Physiol. 1957,11, 269.

7. Snedecor, G. W. Statistical Methods Applied to Ex-periments in Agriculture and Biology, 5th ed.Ames, Iowa, Iowa State College Press, 1956, p.336.

8. Lagerlof, H., Eliasch, H., Werko, L., and Berglund,E. Orthostatic changes of the pulmonary andperipheral circulation in man. Scand. J. dlin. Lab.Invest. 1951, 3, 85.

9. Eichna, L. W., Sobol, B. J., and Kessler, R. H.Hemodynamic and renal effects produced in con-gestive heart failure by the intravenous adminis-tration of a ganglionic blocking agent. Trans. Ass.Amer. Phycns 1956, 69, 207.

10. Fowler, N. O., Westcott, R. N., Hauenstein, V. D.,Scott, R. C., and McGuire, J. Observations ofautonomic participation in pulmonary arteriolarresistance in man. J. clin. Invest. 1950, 29, 1387.

11. Fowler, N. 0. Discussion in Pulmonary Circulation,W. R. Adams and I. Veith, Eds. New York,Grune and Stratton, 1959, p. 197.

12. Dexter, L., Whittenberger, J. L., Haynes, F. W.,Goodale, W. T., Gorlin, R., and Sawyer, C. G.Effects of exercise on circulatory dynamics ofnormal individuals. J. appl. Physiol. 1951, 3, 439.

13. Fowler, N. O., Westcott, R. N., Scott, R. C., andMcGuire, J. The effect of nor-epinephrine uponpulmonary arteriolar resistance in man. J. dlin.Invest. 1951, 30, 517.

14. Patel, D. J., Lange, R. L., and Hecht, H. H. Someevidence for active constriction in the human pul-monary vascular bed. Circulation 1958, 18, 19.

15. Burton, A. C. Discussion in Pulmonary Circulation,W. R. Adams and I. Veith, Eds. New York,Grune and Stratton, 1959, p. 71.

16. Burton, A. C. On the physical equilibrium of smallblood vessels. Amer. J. Physiol. 1951, 164, 319.

17. Garcia-Ramos, J. On the dynamics of the lung'scapillary circulation. I. The mechanical factors.Amer. Rev. Tuberc. 1955, 71, 822.

18. Connolly, D. C., Kirklin, J. W., and Wood, E. H.The relationship between pulmonary artery wedgepressure and left atrial pressure in man. Circulat.Res. 1954, 2, 434.

19. Mattson, S. B., and Carlens, E. Lobar ventilationand oxygen uptake in man. J. thorac. Surg. 1955,30, 676.

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20. Sundin, T. The effect of body posture on the uri-nary excretion of adrenaline and noradrenaline.Acta med. scand. 1958, 161, suppl. 336.

21. Luft, R., and von Euler, U. S. Two cases of pos-tural hypotension showing a deficiency in releaseof nor-epinephrine and epinephrine. J. clin. In-vest. 1953, 32, 1065.

22. Zweifach, B. WV. General principles governing thebehavior of the microcirculation. Amer. J. Med.1957, 23, 684.

23. Elmadjian, F., Hope, J. M., and Lamson, E. T.

Excretion of epinephrine and norepinephrine un-der stress. Recent Progr. Hormone Res. 1958, 14,513.

24. Hershey, S. G., Zweifach, B. W., and Metz, D. B.An evaluation of the protective action of autonomicblocking agents in peripheral circulatory stress.Anesthesiology 1954, 15, 589.

25. Cander, L., and Forster, R. E. Determination ofpulmonary parenchymal tissue volume and pul-monary blood flow in man. J. appl. Physiol. 1959,14, 541.

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