vq en prono

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Regiona l vent ila t ion-perfusion distr ibution

is more uniform in the prone position

MARGARETA MURE ,1 K A REN B . D OM I N O,2 S T EN G . E. L I N D A HL , 1

MIC HAEL P. H LASTALA,3 WILL IAM A. ALTEME IE R, 3 AN D ROB B W. G L EN N Y3

1Departm ent of Anesthesiology and I ntensive Care, K arol in ska H ospital and I nsti tut e,

SE-171 76 Stockholm, Sweden; and Departments of 2Anesthesiology and 3Medicine and Physiology

and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195

Mure, Margareta, Karen B. Domino, Sten G. E. Lin-dahl, Michael P. Hlastala, Willi am A. Altemeier, andRobb W. Glenny. Regional vent ilation-perfusion distribu-tion is more uniform in the prone position. J. Appl. Physiol .88: 10761083, 2000.The ar teria l blood P O2 is increased int h e p r o n e p o s i t i o n i n a n i m a l s a n d h u m a n s b e c a u s e o f a nimprovement in ventila tion (VA) and perfu sion (Q) ma t ching.However, the mechanism of improved VA/Q is unknown. This

experiment mea s ured regiona l V A

/Q

het erogeneit y a nd t hecorrelation between VA a n d Q in supine a nd prone positionsin pigs. Eight ket a mine-dia zepa m-a nes t het ized, mecha ni-c a ll y v en t i la t e d p ig s w e r e s t u d i ed i n s u pi n e a n d p r on e

positions in ra ndom order. Regiona l VA a n d Q w ere mea s uredus ing fluores cent -la beled a eros ols a nd ra dioa ct ive-la beledmicrospheres, respectively. The lungs were dried at total lungcapacity and cubed into 603967 small (1.7-cm 3) pieces. I nthe prone position the homogeneity of the ventilation distribu-tion increased (P 0.030) an d th e correlation betw een VA a n dQ increased (correlation coefficient 0.72 0.08 a nd 0.82 0.06 in supine a nd prone positions, respectively, P 0.03).The homogeneity of the VA/Q dis t r ibut ion increa s ed in t heprone position (P 0.028). We conclude that the improve-m e n t i n VA/Q ma t ching in t he prone pos it ion is s econda ry

to increased homogeneity of the V

A distribution and increasedcorrelation of regional VA a n d Q.

a eros ol; fluores cent micros pheres ; pulmona ry blood flow -ventilat ion heterogeneity

ARTERIAL BLOOD OXYGENATION is often improved in theprone position in anima ls and huma ns with norma l andinjured lungs (1, 8, 10, 14, 16, 1820, 31). The proneposition improves oxygenation by improving ventilation-perfusion (VA/Q) m a t c h in g , a s m ea s u r ed b y t h e m u l -tiple inert gas elimination technique (MIGET) (1, 8,18). Using single-photon emission-computed tomogra-

p h y, L am m e t al . (14) fo u n d th at th e p ro n e p o stu redecreased VA/Q heterogeneity in dogs with norma l andoleic acid-injured lungs. However, the mechanism ofthe decreased VA/Q heterogeneity in th e prone positionis unclea r. I f VA a n d Q distributions can be character-ized as norma l distributions in the loga rithmic domain,the expected var iance in VA/Q can be described by VA,

Q, a n d t h e corre lat ion b e twe e n th e m . U sin g th is re la-t ion sh ip, Wilson an d B e ck (33) p ostu lat e d t h at th eVA/Q distribution is more uniform in th e prone tha n inthe supine postur e primar ily beca use of more uniformdistributions in VA a n d Q in the prone posture. They

assu m e d th at th e co rre lat io n b e twe e n VA a n d Q w a sless in t he prone position but tha t t his ha d little impacto n th e VA/Q distribution because of the uniformity inVA a n d Q. Th e p r e se nt ex pe ri m en t i s t h e fi r s t t omeasure regional VA/Q distributions a nd correlat ion ofregional VA a n d Q in the supine and prone position,th us directly t esting t he model of Wilson and B eck.

METHODS

This study represents a further analysis of data collectedf r om s ev en of e ig h t a n i m a l s b y M u r e e t a l . (1 8), w h i chdescribed th e influ ence of a bdominal dist ension a nd positionon p ul m on a r y g a s e xc ha n g e b y u s e o f t h e M I G E T. O n ea ddit iona l a nima l w a s a dded t o t he pres ent s t udy. Only da t afrom t he cont rol condit ions a re a na lyzed in t his s t udy, a ndregional VA/Q dis t r ibut ion da t a w ere not a na lyzed a s pa rt ofthe original st udy.

Animal preparation and experimental protocol. The studyw a s a pproved by t he U nivers it y of Wa s hingt on Anima l Ca r eCommitt ee. The anim al prepara tion and experimenta l proto-col were described in detail in the earlier publication (18).B r i e fl y, t h e i n ve st i g a t i on w a s p er f or m e d i n e ig h t 3 0- t o45-da y-old pigs [15.4 2.0 (SD) kg body wt (ran ge 1320 kg)].The pigs were health y a nd free from significan t diseases. Thepigs were allowed to eat a nd drink a d libitum until premedica-t ion, w hich cons is t ed of a n int ra mus cula r inject ion of xyla -zine (2 mg /kg) a nd keta mine (20 mg /kg) given 10 min beforet he s t a r t of t he inves t iga t ion. A nes t hes ia w a s induced w it hket a mine (20 mg/kg iv) a nd dia zepa m (0.5 mg/kg iv) a ndcon t i n u ed w i t h a m i xt u r e of d i a z ep a m (1 .7 m g /m l ) a n dketa min e (67 mg/ml) at 4 ml/h. Anest hetic a gent s for ma int e-nance were given in sufficient doses to prevent spontaneous

ventilat ory effort a nd to maint ain a sur gical plan e of anesthe-s ia . No mus cle rela xa nt s w ere us ed. Aft er t ra cheot omy a ndendotrachea l tube insertion, all pigs were mecha nically venti-lat ed with a fractional inspira tory O2 of 0.4 an d a t idal volumeof 15 ml/kg a t a res pira t ory ra t e t o a chieve normoca pnia .B ody t empera t ure w a s a djus t ed t o norma l w it h hea t ing pa ds .

One a rt eria l ca t het er w a s ins ert ed int o t he ca rot id a r t eryt o monit or mea n s ys t emic blood pres s ure a nd hea rt ra t e a ndan other into the femoral a rtery for blood-ga s sam pling (modelABL 4, Radiometer, Copenhagen, Denmark). A 5-F pulmo-n a r y a r t e r y c a t h e t e r w a s i n s e r t e d v i a t h e i n t e r n a l j u g u l a rv e i n t o m e a s u r e b o d y t e m p e r a t u r e a n d c a r d i a c o u t p u t i ntriplicate (Edwards COM 2, Baxter, Irvine, CA). Pulmonary

The costs of publication of this article were defrayed in part by thep a y m e n t of p a g e c h a r g es . Th e a r t ic le m u s t t h e r ef or e b e h e r e b ymarked advertisement in accordan ce with 18 U.S.C. Sect ion 1734solely to indicate this fact.

J. Appl. Physiol.88: 10761083, 2000.

8750-7587/00 $5.00 C opyr igh t 2000 the American Physiological Society1076 h t t p://w w w.ja p.or g


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From t hes e da t a , s t a nda rd devia t ions of VA a n d Q distribu-t i on s w i t h r e fe r en ce t o l og VA/Q (log S D VA a n d l o g S D Q,respectively) were calculated (3). Log SD VA reflects het eroge-neit y in t he VA distribution with reference to VA/Q. Log SD Qreflects heterogeneity in the Q distribution with reference toVA/Q. Thes e va lues a re t herefore s imila r in concept t o logS D VA and log SD Q derived from MIGET(9, 30).

Statistics. Slopes of linear gradients from all animals werecompa red w it h zero w it h a s ingle-s a mple t w o-t a iled

t-test.

Differences in all heterogeneity data and flow gradients fromall animals were compared in supine and prone positions bytw o-ta iled paired t-tests. Differences in the correlation coeffi-cient w ere compa red us ing F is hers z t ra ns forma t ion. P 0 .0 5 w a s c on s i de r ed s t a t i s t i ca l l y s i gn i fi c a n t . Va l u e s a r em e a n s S D .

RESULTS

H e m od y n a m i cs a n d r e sp ir a t o r y v a r i a b le s a r e p re -sented in Ta ble 1. Arteria l P O2 (P a O2) in cre ase d an dalveolar-arterial P O2 difference decreased in the proneposition (P 0.03). Otherwise, there were no differ-ences in these var iables between the supine and pronepositions.

Th e n u m be r of l u ng p iece s a n a l y ze d p er a n i m a lra nged betw een 603 and 967 pieces, w ith 1214 right-to-left planes, 1013 dorsal-to-ventral planes, and 1621 caudal-to-cranial planes. There was considerableisogra vita tional heterogeneity of the VA an d Q distribu-tions (Fig. 1). The coefficient of va ria tion of VA w a sd ecr ea s e d i n t h e p r on e com p a r ed w i t h t h e s u pi n eposition (P 0.012; Table 2). Although the coefficient ofva riat ion of Q decreased, it was not statistically signifi-c a n t (P 0.11; Table 2). VA was in cre ase d in ve n tralregions in both positions (Fig. 1), a s refl ected by d orsa l-t o-v en t r a l (v er t i ca l ) g r a d ie nt s g r ea t e r t h a n z er o(Ta ble 2). VA was in cre ase d in th e cran ial co m p are d

with th e cau d al re g io n s in th e su p in e p o si t io n (P 0.01; Ta ble 2). The vert ical g ra dient in VA in th e supinep osit ion re m ain ed af te r corre ction for tre n d s in th ecauda l-to-cra nia l dimens ion (Ta ble 2). The ma gnit udeof th e ca uda l-to-crania l gra dient in VA decreased (P 0.03) in th e pr one position (Ta ble 2). Q te n d e d to b ein cre ase d in d o rsal an d cran ial re g io n s in th e su p in eposition (Fig. 1), although the dorsal-to-ventral (verti-

cal) an d cau d al- to - cran ial g rad ie n ts we re n o t s ig n ifi -can t ly d i ffere n t f rom z ero (P 0.18 an d P 0.15,respectively). However, the vertical gradient in Q be -cam e sig n ifi can tly d i ffere n t f rom z ero in th e su p in eposition, after correction for trends in the caudal-to-cran ial d im e n sio n (P 0.004; Ta ble 2). In contr a st,there w ere no vertical or cauda l-to-crania l gra dients int h e Q d istr ibu tion in th e p ron e p osi t ion . VA a n d Qt e n de d t o d ecr e a s e i n t h e p er i ph er a l l u ng r eg ion s(Fig. 1), but w hen norma lized by piece weight a nd mea nven ti lat io n o r flo w, re sp ective ly, th is tre n d wa s n otobserved.

Ta ble 1. H emodynamic and respir atory vari ables

S u pine P r one

Ventilation

Pla teau pressure, cmH 2O 13 3 13 3VT, m l 197 42 196 30Com plia nce, ml /cmH 2O 15.2 3 15.5 2.8RR , br ea t h s/m in 27 2 26 3

Hemodynamics

H R, bea t s/m in 109 16 105 19P sa , m m H g 94 21 103 19P p a , c m H 2O 25 6 26 6Pw, cmH 2O 10 6 9 5

Q, l/m in 2.6 1.0 2.2 0.7Gas exchange

P AO2 P a O2, Tor r 52 26* 23 13*P a O2 , Tor r 193 45* 223 29*P a CO 2 , Tor r 39 4 40 3P vO2, Tor r 42 7 44 7pH 7.38 0.07 7.38 0.09

Values a re means S D ; n 8. Fract ion of inspiratory O 2 0.40.VT, t id a l v olu m e ; R R , r e s p ir a t or y r a t e ; H R , h e a r t r a t e ; P s a , m e a nsystemic arterial pressure; Ppa, mean pulmonary arterial pressure;Pw, pulmonary capillary wedge pressure; Q , blood fl ow; P AO2, alveolarP O2 ; P a O2 , arterial P O2 ; P a CO 2, arterial P CO 2; P vO2, mixed venous P O2 .*S ignificant ly different from supine, P 0.05.

Fig. 1. Ventila t ion (VA; A) and perfusion (Q ; B) a s a f u n c t ion ofdorsal-to-ventr al dist an ce in supine and prone position in a represen-tat ive pig. Independent and dependent a xes have been interchangedfor presentat ion. VA a n d Q are plot ted for each lung piece at eachplane in dorsal-to-ventral (y) directions. Solid line, linear regressionequation. Drawings of lungs serve as schematics to signify position ofp ig a n d a r e n ot a c cu r a t e r e pr e s en t a t ion s of lu n g s h a p e. L in e a rregression equations for VA vs. dorsal-to-ventral distance: VA 0.43(cm of lung) 2.18 (r 0.31) in supine position an d VA 0.27 (cm oflung) 2.29 (r 0.25) in prone position. VA in ventra l lung regionswas increased in both posit ions, a lthough considerable isogravita-

t ional VA heterogeneity wa s present . Linear regression equat ions forQ vs. dorsal-to-ventral distance: Q 0.2 (cm of lung) 4.44 (r 0.21) in supine position an d Q 0.1 (cm of lung) 2.22 (r 0.13) inprone posit ion. In supine posit ion, Q tended to be higher dorsally,a lthough t here wa s considerable isogravita t ional heterogeneity.

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The VA/Q distribution a lso ha d signifi cant isogra vita -tiona l heterogeneity ; however, VA/Q ratios became moreuniform w hen th e an ima ls w ere prone (Fig. 2, Ta ble 2).In the supine position there w ere significant dorsal-to-v en t r a l (P 0.002) a nd cauda l-to-crania l gr a dients

(P 0.004) in log VA/Q (Fig. 2, Ta ble 2), such t ha t VAwas re lat ive ly in cre ase d co m p are d with Q i n v e nt r a la nd cra nia l lung r egions (Fig. 2, Ta ble 2). The vert icalg r a d i en t r e ma i n ed a f t e r cor r e ct i on of t r e nd s i n t h ecauda l-to-crania l direction (P 0.001). In contr a st,there was no dorsal-to-ventral (vertical) gradient of logVA/Q in t he prone posit ion (Fig . 2, Ta ble 2). The vert ica lg rad ie n t an d cau d al- to - cran ial g rad ie n ts o f lo g VA/Qd ecr ea s e d i n t h e p r on e com p a r ed w i t h t h e s u pi n eposition (P 0.002 an d P 0.005, respect ively ; Ta ble 2).

The heterogeneity of the VA distribution, measuredby

VA

2, d e cre ase d in th e p ron e p osi t ion (P 0.03;

Ta ble 3). In contra st , th e heterogeneity of the Q distri-b u tion , m e asu re d b y

Q

2, d id n o t ch an g e sig n ifi can tly

(P 0.18; Ta ble 3). C orrelat ion betw een regional VAa n d Q increased in the prone position ( 0.82 0.06a nd 0.72 0.08 in prone a nd supine positions, respec-

tively, P 0.03; Fig. 3, Table 3). VA/Q heterogeneity, as

measured by VA/Q

2, decreased in th e prone position (P

0.028; Ta ble 3). The va ria ble of VA/Q

2calculated indirectly

by Wilson and Beck (33), VA/Qcal

2, was identical to the ob-

served variance of VA/Q (VA/Qobs

2; Ta ble 3).

When t he heterogeneity of th e VA an d Q distributionswa s compar ed wit h reference to log VA/Q ra tios (Ta ble4), calcula ted a ccording t o Altemeier et a l. (3), th e pronep os it i on w a s a s s oci a t e d w i t h a l ow e r l og S D VA (P 0.010) and log SD Q (P 0.015). The heterogeneity ofVA/Q d istr ib u tio n , m e asu re d b y lo g S D VA/Q, w a s a l s olower in t he prone position (P 0.016; Ta ble 4).

DISCUSSION

The major fi nding of this study is t ha t VA/Q distribu-tion became more uniform in the prone position be-

cause of an increase in homogeneity of the VA distribu-tion an d a n increase in correlat ion betw een regiona l VA

a n d Q.M eth odological i ssues. Before discussing the signifi-

cance of these fi ndings, we ha ve to consider the limita -tions of the met hods used. The lungs w ere dried ex vivoa t t ota l lung capa city, giving a ll alveoli uniform size. Toe stim at e re g ion al b lood flo w re liab ly, th e rad io activemicrospheres need t o be tota lly tr a pped by the pulmo-nary microcirculation. Microspheres with a 15-m diam-eter are almost completely entrapped by the pulmonarycirculation (25) and a dequa tely refl ect the dist ributionof blood flow (6, 16). St udies compa ring t he dist ribut ionof N,N,N-trimethyl-N[2-hydroxy-3-methyl-5-iodoben-zyl]1,3-propanediam ine, a diam ine w ith a near-com-

p le te fi rst- p ass e xtractio n b y th e lu n g s, h ave sh o wnth at th e p rin cip le u se d in th e p re se n t s tu d y re fle ctsregional pulmona ry blood fl ow (16).

With use of similar reasoning, instead of radioactivemicrospheres for ca lculat ion of lung perfusion, a erosol-iz ed flu o resce n t m icro sp h ere s we re u sed to m e asu reventila tion. The fluorescent s igna ls were recently s hownb y R ob er t s on e t a l . (26) a n d M el s om e t a l . (17) t orepresent VA. We therefore employed the method de-scribed by Altemeier et a l . (3) to simult a neously m ea-sure regional VA a n d Q in 1.7-cm 3 cubes of lung withmicrosphere techniq ues.

F ig . 2 . L og VA/Q as a function of dorsal-to-ventral (y) distance ins u pin e (A) a n d p r o n e (B) p os it i on i n s a m e p i g u s ed i n F i g. 1.Independent and dependent axes have been interchanged for presen-tat ion. Linear regression equat ions: log VA/Q 0.14 (cm of lung) 0.6 (r 0.64)in s upine position an d VA/Q 0.01 (cm of lun g) 0.31(r 0.07) in prone position. In su pine position, log VA/Q wa s lower indorsal and higher in ventral lung regions. Distribution of VA/Q w a smore uniform in prone posit ion, a lthough considerable isogravita-t ional heterogeneity remained.

Ta ble 2. Coefficient of var iat ion and grad ients as l i near fun ction of spati al v ectors

Coeff ofVaria tion, %

Gr a di e nt s

Dorsal-to-ventral(vertical)

Dorsal-to-ventral(cor r ect ed) C a uda l-t o-cr a nia l

Supine

VA 81.6 13.1 0.228 0.351* 0.183 0.230* 0.215 0.180*Q 73.2 6.4 0.083 0.156 0.124 0.084* 0.070 0.122Log VA/Q 0.098 0.058* 0.077 0.039* 0.043 0.028*

Prone

VA 66.8 7.1 0.122 0.135* 0.072 0.099 0.079 0.104Q 67.9 8.8 0.011 0.056 0.019 0.060 0.024 0.088Log VA/Q 0.005 0.021 0.005 0.015 0.003 0.013

Values a re means S D ; n 8. Gra dients for ventila t ion (VA) and perfusion (Q) a r e m l m in1 cm 1; gradients for log VA/Q are cm 1. * P 0.05, grad ient vs. zero; P 0.05, supine vs. prone; P 0.01, supine vs. prone; P 0.001, supine vs. prone.

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B eca use the lungs in this study w ere dissected a longa n orth ogonal grid, periphera l lung pieces a re not fullcubes. Hence, a ll the lung pieces used in th is study a renot uniform in volume. We used w eight norma lizationin t he past to correct for this a rtifa ct. We ha ve chosennot to weight normalize flows in this analysis, becausewe b e lie ve th at re sp irato ry an d in e rt g as e xch an g e isdetermined by the relationship between local ventila-tion and perfusion a nd th eir flow ra tes in milliliters perm in u te . T h e ad d it io n al variab i l i ty in lu n g p ie ce siz eadds to the observed heterogeneity of VA a n d Q. Thev a l ues of VA a n d Q h et e r og en ei t y i n Ta b l e 2 a r etherefore significan tly la rger tha n previously reported.B eca use this increased var iability occurs in supine a ndp ron e p ostu re s, th e re lat ive d i f fe ren ces b etw e en th epostur es remain similar to those presented without useof weight-normalized fl ow s, a nd the conclusions of thestu d y are u n ch an g e d . T h e co rre lat io n b e twe e n lo cal

ve n tilat io n an d p erfu sion is also sl ig h tly in cre ase d :sm all p ie ce s te n d to h ave le ss ve n ti lat io n an d p e rfu -sio n , wh e re as larg e r p ie ce s h ave g re ate r ve n ti lat io na nd perfusion. Although directional gr ad ients in venti-lat io n an d p e rfu sio n are p re se n te d in m il l i l i te rs p e rm in u te p e r ce n tim e te r, we also e xp lo re d th e sp atialdistributions of VA a n d Q af te r we ig h t n o rm aliz at io n.There were no significant differences in the directionalg rad ie n ts b e twe e n w e ig h t-n orm a liz ed fl ows an d flo wsin milliliters per minute.

S p at i a l d i str i b u t i o n s of V A/ Q . D u rin g m e ch an icalve n tilat io n , we fou n d th a t VA wa s in cre ase d to ven tra l

l un g r e gi on s i n t h e s u pi n e a n d p r on e p os it i on s , a sdemonstr a ted by significan t dorsal-to-ventra l (vertical)gra dients (Fig. 1, Ta ble 2). In creased V A to dependentve n tral lu n g in th e p ro n e p o si t io n h as b e e n d e m o n -

strated previously in humans (5, 12, 23) and animals(14). Ou r re sults ar e d i ffere n t f rom th o se in su pin eu n an e sth e tiz ed , sp on ta n e ou sly b reat h in g h u m a n s, inwh o m VA was increased to dorsal, dependent lung (5,12, 22, 24). Th e varia t ion s m ay re fle ct d i ffere n ce sbetween the mechanical and spontaneous ventilation,species differences, an d met hodologica l fact ors, such a su se o f ae ro so ls vs . rad io active - lab e le d g ase s, sp atialre so lu tio n , an d th e lu n g vo lu m e at wh ich ve n ti lat io nwa s normalized. The role of an esthesia a nd mechanicalventilat ion is likely to be quite significant , inasmuch a si t re d u ce d th e g ravi tat io n al g rad ie n t o f VA in supineh u m an s b y in cre asin g ven ti lat io n of n on d ep en d e n tventr a l lung (24).

The increase in Q to dorsa l lung regions in th e supineposition (Fig. 1, Ta ble 2) is consist ent w ith prior work inhuma ns (4, 12, 15, 21) and a nima ls (7, 10, 17, 31). Ourfi ndings of a lack of a vert ical gra dient of Q in th e proneposition (Fig. 1, Ta ble 2) a re simila r t o prior r esults inanimals with use of similar methodology (10, 31, 32).B e ck a n d Re h d er (7) d em on stra te d a h ig h er con d u c-tance for blood flow in dorsal lung regions in the dog,wh ich m ay re sult in a re lat ive in crease in Q to d o rsallu n g re g ion s in q u ad ru p ed an im a ls in d e pe n d en t ofposit ion (7, 10, 31).

Ta ble 3. H eterogeneit y of V A a n d Q d i str i b u t i o n s

AnimalNo.

VA

2

Q

2VA/Q VA/Qcal

2

VA/Qobs

2

S u pine P r one S u pine P ron e S u pin e P r one S u pine P r one S u pine P r one

1 1.27 1.24 1.43 1.04 0.78 0.85 0.59 0.35 0.59 0.352 5.15 1.20 2.12 1.07 0.66 0.90 2.89 0.23 2.90 0.233 2.05 0.71 1.86 1.96 0.81 0.80 0.76 0.77 0.75 0.784 1.35 0.82 1.37 0.99 0.82 0.84 0.50 0.30 0.48 0.30

5 2.99 1.13 1.61 1.18 0.70 0.78 1.55 0.50 1.56 0.486 2.32 0.76 1.26 0.76 0.67 0.74 1.28 0.40 1.28 0.407 1.64 1.57 2.83 2.67 0.58 0.79 1.96 1.02 1.96 1.038 2.39 1.85 1.67 2.35 0.73 0.89 1.14 0.47 1.14 0.47

Mea n 2.39 1.16 1.77 1.50 0.72 0.82 1.33 0.51 1.33 0.51S D 1.25* 0.40* 0.51 0.72 0.08* 0.06* 0.80* 0.26* 0.81* 0.27*

VA

2, Variance of VA distribution;

Q

2, var ian ce of Q distribution; VA/Q , correla tion betw een VA a n d Q distributions; VA/Qcal

2, calculated var iance

of VA/Q distribution; VA/Qobs

2, observed varia nce of VA/Q distribution. * P 0.05, supine vs. prone.

F ig . 3 . VA as a function of Q in each individual lungpiece plotted according to method of Altemeier et al.(3) in same pig used in Figs. 12 (A is supine, B isprone). Regional VA a n d Q are highly correlated inboth positions, although correlation between VA a n dQ is higher in pr one position.



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Our study found vertical a nd cauda l-to-crania l gradi-e nt s i n t h e VA/Q distributions in the supine position,s u ch t h a t VA/Q ra tios w e re lowe r in d o rsal a n d cau d allung regions th a n in ventra l and crania l regions (Fig. 2,Tab le 2). I n th e p ron e p osi t ion th e d istr ibu tion ofVA/Q was more uniform, reflected by a lack of verticaland caudal-to-cranial gradients. Although our resultsa re consistent w ith t hose in an esthetized, mechanicallyve n tilate d an im a ls (14), s tu d ies in u n an e sth e tize d ,

sp on ta n e ou sly ve n ti lat in g h u m a n s h ave d e m on stra te da gravitational dependence of VA/Q, su ch th at VA/Q isi n cr e a s ed i n d ep en d en t l un g i n s u pi n e a n d p r on epositions (12, 22). H owever, the presence of a nesth esiaan d m e ch an ical ve n ti lat ion m ay re verse th is re lat ion -s h ip a n d i ncr ea s e VA/Q t o n on d ep en d en t l un g , a ss h ow n b y L a n d m a r k e t a l . (15). Th i s fi n d in g i s i na g r e e m e n t w i t h t h a t i n t h e p r e s e n t s e r i e s w h e n t h ea nima ls w ere in the supine position. The more uniformdist ribut ion of VA/Q in th e prone position cont ribut es tothe w ell-ma tched VA/Q in th a t p ostu re a n d con sti tu te sthe primary mechanism for increases in Pa O2 (1, 8, 10,18, 19) and improvements in pulmona ry ga s excha ngereport ed in t he prone posit ion (8, 14, 18).

H eterogeneity of V A/ Q . The pr one position increa sedh om og en e ity of th e VA/Q d i st r i bu t i on a s a r es u lt ofincreased homogeneity of the VA d istrib u tio n an d in -creased correla tion betw een regional VA an d Q. Impr ove-

ment in t he uniformity of the VA distribution is consis-tent w ith studies tha t suggest a more even distribut ionof VA in the prone position (1, 5, 14). This spea ksa g a i n st a m a r k e d ov er v en t i la t i on i n n on d ep en d en tregions, as we observed in the supine position. VA m a yb e m o re u n ifo rm in th e p ro n e p o si t io n , b e cau se th epleural pressure gradient is more uniform, inasmuchas there is less change in pleural pressure per centime-ter of distance (20, 34). Although Q heterogeneity didnot change signifi cant ly w ith t he prone position in our

study w ith pigs, increases in t he homogeneity of the Qd i st r i bu t i on h a v e b ee n d em on s t r a t e d i n t h e p r on eposition in dogs (8, 10), sheep (31), and humans (21).Th e l a ck of ch a n g e i n t h e p r es en t s t u d y p r ob a b lyre fle cts in ad e qu ate p owe r d u e to in te ran im al varia b i l-ity, a lthough methodologica l differences a nd speciesdifferences [intensity of the hypoxic pulmonary vasocon-str ictor (HP V) response] may be importa nt. The morei n t en s e H P V r es pon s e i n p ig s (13) m a y a t t e nu a t eposition-related differences in Q heterogeneity. The pres-ent st udy uniquely demonstra tes a n improvement in thecorrela tion of regiona l VA a n d Q in t he prone position.

Wilson an d B e ck (33) sp eculate d th a t th e p ron eposition decreases VA/Q heterogeneity by improvedhomogeneity of the VA a n d Q dist ribut ions. They postu-l a t e d t h a t t h e VA distribution wa s more uniform in th ep ron e p os i t ion , b eca u s e t h e r e i s n o g r a v it a t i on a l l yr el a t e d p leu r a l p r es s ur e g r a d i en t . O n t h e b a s i s ofstudies in the dog, they estimat ed tha t t w o-thirds of thev a r ia n ce i n VA/Q i s a r e su lt of n on u n if or m Q a n done-third is the result of nonuniform VA. Wilson andBeck reasoned that regional VA a n d Q m u st b e we a k lycorrelat ed in the prone position, beca use VA a n d Q donot share a gravitational influence. Although the scaleof measurement (1.7 cm 3) used in t he present study iscon s id er a b l y l a r g er t h a n s om e o f t h e d a t a u s ed b yWilson and Beck, their model is not scale dependent.The variance we observed in the distribution of VA/Q(

VA/Qobs

2) exactly equa led the var iance in VA/Q predicted

by t he their model (VA/Qca l

2) in bot h posit ions (Ta ble 3).

However, the magnitude of the variance was consider-ably larger (Ta ble 3) than wa s estima ted by Wilson a ndB e c k . I n a d d i t i o n , t h e v a r i a n c e o f r e g i o n a l V A w a s

larger t ha n the var iance of regional Q, in contra st t o theprediction for dogs (33). This difference in result s m a ybe due to species differences, scale of measurement, orcomparability of techniques used to measure regionalVA a n d Q. Dogs, wh ich ha ve extensive collat eral vent i-la tion (13), ma y ha ve a more homogeneous distribut ionof v en t i la t i on t h a n p ig s . I n a d d i t ion , v en t i la t i on i n1.7-cm 3 lung pieces is primarily dependent on convec-tive g as m o ve m e n t, wh e re as in sm alle r u n its o f m e a-surement, gas diffusion dominates. Wilson and Becka lso relied on different m ethods to mea sure regional VA(e.g. , parenchymal density, external detectors) and Q(e.g., m icrospheres ).

Ahigh correlation between regional VA a n d Q, a s w a sd em on s t r a t e d i n t h e p r es en t s t u d y, h a s a l s o b e enobserved using identical methodology in the prone pig(26). Alth ough counter to t he prediction of Wilson a ndBeck (33), an excellent correlation of regional VA/Q isnot surprising because of the importance of anatomicstructur e in determining regiona l Q (10), a nd probablyVA, an d p h ysio lo g ical m e ch an ism s, su ch as HPV an dcollat era l vent ilat ion, which act t o improve VA/Q m atch -ing on the local level. I t is possible, however, that V Aa n d Q correlat ion ma y be lower w hen a sma ller scale ofmeasurement is used.

Rela ti onshi p wi th M I GET-der iv ed ind exes of heter oge-neity. The microsphere method ha s a n a dvan ta ge over

trad it io n al m e asu re m e n ts o f g as e xch an g e , in th at i tprovides spatial measurements of regional VA, Q , a n dVA/Q. Ho we ver, m icro sp h ere -m e asu re d d a ta m ay b eco m p are d with d ata f ro m m o re trad i t io n al m e th o d s,s u ch a s M I G E T w i t h a p pr op r ia t e t r a n s f or m a t i on . I nthese experiments, log SD Q a n d l o g S D VA calculatedfro m th e m icro sp h e re d ata we re le ss th an th e p re vi-ously reported results using MIG ET (18). This repre-s en t s a n u n d er e st i m a t i on of VA/Q heterogeneity bym icrosp h ere s or an overe stim ation b y M I G E T. Th em icrosp h ere m e th od m ay p ote n tial ly u n d ere stim atetru e VA/Q heterogeneity because of its resolution limit

Ta ble 4. H eterogeneit y of V A , Q , and V A/ Q di str ibuti ons wi th referenceto l og V A/ Q r a t i o

S u pin e P r one P

Log SD VA 0.798 0.252 0.514 0.143 0.010Log SD Q 0.603 0.205 0.398 0.065 0.015Log SD VA/Q 1.110 0.339 0.691 0.177 0.016

Values a re means S D ; n 8. Log SD VA, s tanda rd deviat ion of VAd is t r ib u t ion w it h r e fe r en c e t o log VA/Q r a t io ; log S D Q , s t a n d a r d

d e via t ion of Q d is t r ib u t ion w it h r e fe r en c e t o log VA/Q rat io; logS D VA/Q , s tan dard deviat ion of log VA/Q distribution.



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of 1.7 cm 3. Observed heterogeneity of regional perfu-sion in cre ase s in a p red icta b le fash ion as re solu tionincreas es (11). S imila rly, the observed h eterogeneity ofventilat ion increa ses as resolution improves at least t oa nd likely beyond the resolution obta ined in this st udy(2, 27). Given t he relat ionship betw een the va ria nces oft h e VA/Q, Q, a n d VA d istrib u tio n s d e fi n e d b y E q . 4 ,improved resolution will increase the observed hetero-g e n e ity o f th e VA/Q d istr ibu tion , u n less th e re g ion alcorrelat ion between VA a n d Q increases. Alternatively,M I G E T m ay o vere stim ate th e tru e VA/Q heterogeneityb ecau se o f airw ay e xcretion of h ig h ly solu ble g a se s(28, 29) or because of enforced smoothing of the V A/Qdist ribut ion. This effectively limits how different Q a n dVA d at a p oin ts can b e assig n ed t o com p artm e n ts withsimilar VA/Q ratio s.

Al t em ei er et a l . (3) f ou n d t h a t m ea s u r em e nt ofregiona l VA/Q wit h microspheres more accura tely pre-d icte d Pa O2 a n d a r t er ia l P C O2 t h a n M I G E T in n o r m a llu n g s, a l th o u g h m icrosp h ere s u n d ere stim ate d ar e aswith low VA/Q ratios after administration of glass emboli

(3). The correla tion betw een measur ed (by MIG ET) a ndp red icte d (b y m icrosp h ere s) in ert g as re te n tion wa sh ig h (r 0.99) in normal lungs (3). These r esults

suggest tha t, in the norma l lung, ana lysis of regiona l VA/Qwith aerosolized and injected microspheres is a validm e th od to stu d y p u lm on ary g as e xch an g e a n d h a s th eadvantage of providing high spatial resolution (3).

Although P a O2 increased in the prone position in thepresent study, MIG ET indexes, including log SD Q, logS D VA, an d th e arte rial- alve o lar d i f fe re n ce are a, we renot significantly different with control conditions (18).I n co n trast , we o b se rve d sig n ifi can t d e cre ase s in lo gS D VA, log S D Q, a n d l og S D VA/Q derived simulta neouslyusing microspheres. The lack of sensitivit y of MIGE Tt o

detect sma ll, but physiologica lly significan t, cha nges inVA/Q h e t e r o g e n e i t y i n t h e n o r m a l l u n g m a y b e t h er e su lt of e rr or s i n du ced b y M I G E T a l gor i t h m s a n dsmoothing procedures a nd/or a irw a y excretion of highlysoluble gases (29). Comparison of gas exchange datad e rive d fro m m icro sp h e re s in th is s tu d y to th e g as-exchange indexes measured by MIGET (18) suggeststh at th e m icro sp h e re te ch n iqu e m ay p o sse ss g re ate rse n si t ivity to d e te ct ch an g e s in VA/Q i n t h e n o r m a llung.

The present study nicely illustrates that changes inlog SD Q, a s obta ined using MIG ET, do not necessarilym e a n t h a t r eg ion a l Q ch an g e s. I n asm u ch as lo g S D Q

re fle cts th e varian ce o f th e Q

distribution with refer-ence to t he VA/Q ra tio, a ch an g e in th e VA distributiona nd/or correla tion of VA a n d Q wil l ch an g e lo g S D Q,ev en i f t h e Q d istr ibu tion is u n ch an g e d . A sim ilarre aso nin g a p plie s to th e VA distribution for log SD VA.Therefore, inferences a bout changes in the regiona lVA or Q distributions cannot be accurately made usingMIG ET-derived va ria bles. In a ddition, a more homog-enous VA or Q distribution does not necessarily meanimproved arterial blood oxygenation or decreased VA/Qh e tero ge n eity. A u n iqu e ad va n ta g e of m icro sp h ere -

derived VA/Q distributions over MIGET is, therefore,

the ability to determine the mechanism for the changein VA/Q matching, i .e . , changes in regional VA distri-

bution, regional Q dist ribut ion, a nd/or correlat ion of

regional VA a n d Q.In summa ry, the VA/Q distribution wa s more uniform

in an e sth e tiz e d , m e ch an ical ly ve n ti late d p ig s in th eprone position. The homogeneity of th e VA distributionwas in cre ase d , an d co rre lat io n o f VA a n d Q w a s i m -proved.

Th e a u t h or s g r a t e f u lly a c k n ow le d ge t h e e xc el len t s e cr e t a r ia lassistan ce of L. H ubbard-Ha macher a nd th e expert technical help ofD. An, E. Anderson, and Dr. S. Bernard in completion of the studies.

T h is s t u d y w a s s u p p or t e d b y N a t ion a l H e a r t , L u n g , a n d B loodInst itute Grants HL-12174 and HL-24163, The Swedish Heart andL u n g As s oc ia t ion , a n d Th e S w e d ish S ociet y of M e d icin e (Ca r inTry gger s Minn esfond).

Ad d r es s f or r e pr in t r e q u es t s a n d ot h er c or r e s pon de n ce : K . B .Domino, D ept . of Anesthesiology, University of Washington, Box356540, Seatt le, WA 98195-6540 (E-mail: [email protected] shin gton .edu).

Received 8 April 1999; a ccepted in fi na l form 25 October 1999.

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