Ventilation-perfusion relationships in alligators

83

Re.~}~iruricm Phv~io~ovv. 78 (1989) 8 3 - 9 4 Kiscvi~r

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Ventilation-pedusion relationships in alligators F r a n k L. Powell a n d A n d r e w

T. Gray

Deparmwm of Medicine, University ~ California, San Diego. La Joi]a, CA 92093, U.S.A. (Accepted for publication 10 June 1989) AbstraeL We measured "/,'Q distributions with the muluptc inert gas elimination technique in five ancsd~e~.ized artificially ~cn~ilatcd American afligators at 24" C, The overall '~','0 was rdatively high (2,0 to 7.2) becaus~~ of c.n.tmuous artificm} ventilation. The ~',Q distributions were usually unimodal (iog standard deviation o f ( ) distribution averaged 0.47 ± 0,09 [SD]) and there was considerable shunt (28,5 ± 10.3~'. of cardiac output). 1 h e data are consistent with a pulmonary, rather thm', central cardiovascular s h a m We atso de~.ected a molecular weight dependent limitation to inert gas e~iminatmn. The difference in error of fit to enflurane and cyc]opropane relentmns ;va~ sigmficandy greater than predicted from experimental error. The est~ma:ed stratification diffusing capacity, a measure of this limitation, ~ a s 10°o of the value estimat~zd !'or mammals and similar to morphometric estimates of m e m b r a n e diffusing capacity in Mfigators, -. ....... ~ ~..m,. . . . . . . . . . . . , ..... H . . . . . . c. -~. . . . . .,,~ . . ,.. ~,-~, =, t-,,eo ~., .-,,e=0o, s are unevenly }...,~"'*".,.~,,,vaa"~ a and have !argc gas phase diffusion spaces, '~'.0 matching and molecuiar ~smDht dependent limitations are reiati~ el> small. Shunt, dead space and m e m b r a n e diffusion resistances can be more important limitations of gas exchange.

D~f}2~s~on; Iner~ gas, Intrapu!monar 5 gas mixing: Multicamerai lung: Straufication

Little is known about the spafia! matching of pulmonary ventilation and blood flow in air breathing i< ~ver ',:rtebrates. In mammals (FaQi, 1987} and birds {Powdt and Scheido ~989} ILls typ: of inhomogeneit2. is the major timkation to gas exchange under re~ting normoxic con~itions. Studies on distributions of ventilation-perfusion ratios {';' Qt m oJv:r ve~ebrates are Iimited to reptiies with unicameral ~ungs like the carpet python tDonneitv and Woolcock. i 9 7 8 ) a n d Tegu lizard (H!astala elM.. 1985). The meani~.e of V Q inhomo~zeneiv, for such one c o n m a n m e m i,,-os is somewhat differen! than for mukicompartn~enta] lungs iike the ed,-.eolar lungs ofMammaiia, parabronchial lungs of.4 yes or mu!ficamera! iunes cd" many reptiles. V.(O inh~,rnoaeneitv measured in unicamera} lungs mus~ imply stratification of ventilauon or perfusion u i".hin a compartment ins~e:~d of unequal co~>ecfive flows be~we,zn compartments. i o understand the comparative ph3. sioiog.~, efgas exchange iimkations from inhomo•aeneities be~t,:r, a e measured V.Q distributions in fne :~mcncan~ "~ " ±l;oa~o~.,~.,usina~ the C,-,~'re~?o,~O~'~.,ce .:da~e'<~ Dr. Yx'ank L~ Pompeii. D e p . r ~ m e ~ Caii!\wm;~. Sa~: E,he~o. La Joi~a. CA 92693,. L' S..a..

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muitiph~ inert gas eiimination technique. Alligators are an interesting model for this prob{em for ~evcra] r~aaons. First. C r m o d i l i a have a multicameral hmg that is heterogem:~)usly pa~ , 6 o n e d into ~,ull,,~.th,,. are more like m a m m a l i a n a,~e¢ , , e than the faveoli (~f s~m:e simpler paucicamerat and multicameral reptilian lungs (Duncker, i978). Sc-eond. they have ,~ complete ventricMar septum reducing the magnitude o f central ,:;~rdu~v;~:,cuiar right..Mt shunts under most conditions (White, i969 and see Discuss~,~). \Vher~ large aimnts do not dominate gas exchange efficiency then 9 / Q mishmtch is potentially a major gas exchar~ge limitatio,a. FineOly, Crocodilia are the first vertebrate:, to show diaphragnatic-like inspiratior~ (Duncker, 19781. Diaphragmatic breathing :n m a m m a l s resu!ts in nonuniform distr.'hutions o f inspiratory forces and vemi!atio~_ (Milic-Emilk 1979).

Xie|ho~ \Ve studied (i've American alligators ( , 4 g ~ a w r mtss~,:,q~pwns~o " ~ . . . . obtained from the >,oc~;etetmr % ~dh~e Rc,u~e, G r a n d Chenier, LA. Animals ranged ~¥om 1.3-3.3 kg body ;veh-~.hk~2.07 ..~'~,aver,.~e.~ The animals were kept outdoors in a fenced enclosure less ,h~..,,.,, one mile fl'om the beach at La Jo!la, CA with areas for water immersion and sun basking. The animais were fed once a week with caif livers, kidneys and fish. kmm.~ds were studied in the supine position at r o o m temperature ( 2 2 - 2 4 : C ) . Cad~e~.ers were placed in the femoral artery and vein using a local anesthetic. While momtoriae pressure in the femoral m"~ery (Statham P23 ID), pentobarbital was administered rm t , e ~cnc, us ,~atue~e, u , m , l e animals reached a surgical plane of anesthesia ~. ,,- ..... .m,~.k~L~_~,\ e mtubated the anima!5, with a pediatric cuff~-d endotracheal tube (size 4F} and mechanicMN ventilated them (Harvard 607}. Frequency fiR) and tidal volumes (V~ } were adjusted in the range reported for awake alligators during a ventilator;,' period :,.~. i*" " ac'; ' ,'~ ,e.. " 19~q~) so .~ad "~ -"exI.lrea " ~ " * F~ .:~. measured with a mass spectrometer (Perkin ..o,~.,v,. t l{m) ~,.as 0.0!--0.02. Venti!ation (V) was measured with a Fleisch ~; :e~.,~taci.,ograph {size 00) and differential pressure transducer (Vatidyne MP45, 2 cm }~}:C) dia~hra~zm), ca~.~'.rated , ~ ~ '~ " with room air at _+ 4.0 L/min. Vr was obtained by d e c ~mtc:d,.. integrating the ventilation signal (Gould 11-4307-159). Once the arlmai was ~°~.~-*;~c~,~,,:,~:"m .:~ ventiiated we opened the 'h~;~,,, . . .ax . w,th:"a. . .e~nu . . . . al imu,me :-': ;~wi:d,m ~.~_,-~ n-~.-;~,,~.. .the . . . . .h-._.a~ . ;. and great vessms in the oericardium The pericardium was ope,..~ed and a 1.25 inch 20 gauge m~giocath was inserted in the pulmonary., artery. for sa~:npliag mi×.ed venous blood. All catheter placements were verified upon necropsy. {' Q di, tribuuons were determined with q~e muRiple inert gas elimination technique (Wagner, e~ eg.,. ~,c<~.,~.,.,a.~..,. .A . . s ~li~,e so.Mtion containing. S F 6, ethane, cyclopropane. enflu,am.:. "~;'"~"* edger and acetone was infused in the femoral venous catheter at 0.25-1.0(} m~,min (Haake-Buch~er 426-1000). After at least 45 rain ofinfiasion we took -~ m! samples of femoral arteriaI and mixed venous blood, simultaneous!y, in heparinized m~,~chco bzarei glasse..; syringes over the course ~!7 aeveral breaths. Mixed expired gas ,...-.-'..,~r~. ..,,. . ,.ve~c .~ake,,. .. a~ me end ef. ,~-~0.9 liter heated metro mixing box after a previously

AL! IGATOR f ,Q

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determined delay, so the gas corresponded to that expired during the blood sampling. FE,.o. and FEo: were also measured in some cases to calculate metab, iic rate. We collected three to six sets of data on each animal with measurements being separated by at least 5 rain. So!ubitifies in duplica!e or triplicate, retentkms (R) and excretions (E) were determined for the ine~ gases using gas chromatograph), (Beckman GC72-5 or Hew!ett-Packau'd 5890A) as previously described (Wagner et al., 1974b; Wagner and Lopez, 1984). All equilibrations necessary, for inert gas analysis were d o n e in a water bath with temperature matched to the body temperature of the animal monitored with a cloacal probe (Yellow Springs Instr. 43TA). Inert gas data were analyzed for V / 0 distributions using the standard alveolar model. To test tbr possible molecular wright dependent hnu.ations, " '" " we studied the errors in fit between measured R and best fit R for indivi ,~.... I.~,-. . . . ¢~vmbolized e ) as proposed by Downs and Wagner (1983). They found the ,. :ex of stratification was the difference between the error in fit to R for t h e . . :rant: 1"185 Do) and the light gas cyclopropane (42 Da). 15xperimcntal error shou!, see. rors for the two gases to vary independentt5 and randomly so their difference. (c e ,:y~:o}, should average ~,.at~.u t,,,~ a a a u , . p . v n using a , , , ~ , , , ~ ,_o~,u ap~.,,,,..-,, | ll~'~glla (:~!J~l ¥ ¥ e!~U:~II~| , 1977). in which we introduced random experimentM e ~ o r to a theoretical set of retentions predicted for a ~//Q distribution typical of that measured in alligators. For 50 such theoretical sets using rain real smoothing (coefficient z = 0. I), (¢ ~,m - e ~:y~-,o) averaged - 0 . 1 9 + 1.0 which ~'; ao~ significantly different than zero. Stratification is predMed m systematically increase this difference (Downs and Wagner, !983) so we tested i\)r a significant moiecular weight dependent limitation by ~es'%_, experimentally - e~ ~ ,) va!ues aeainst zero. e v~as catc~imed as ~i~edifference between mmim.~am ~",~"..~anc~ . . . . R and best fit R predicted fi:,r the '~'/0 distribution: "all values were weighted so experimental error affected them equally (Evans and Wagner, 1977). ..... u,,~. are reposed -± i: SD and signiff'ance taken as Y < 0.05 uMe': otherwise noted.

Ke.v..ahs Some of the meas~.,red variabies were sensitive to d-ie experimental maneuvers. Repea~ed blood samp!ing dq~rc~v-d cardiac omput (OT) and arterial bk;od pressure (table t). QT dropped with the ~.hree pairs of Nood samples. I f 0 T and inert gas eiimination rales also dec~ easea ~,,~,,,.,.,,.~.," ;,,~,~,..mH~ durin~ cc.tlectkm of a blood sample, then some of the inhomogem:it), we ascr%e to paraitc] "{7'Q inequality with our method could include the effects ,of no:~steadv g.ate, biowever, end-tidaJ Fco: decreased only 0.0005 during sampling indicating virtuaily co~lsIant cardiac output. Puimonary O: uptake (~I o: }and CO_, output (M
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Solubilitic.~ o f the inert gases in alligator blood at experiment'~l b o d y t e m p e r a t u r e i 24.,."~ ::. (i. 5 - C) (table 2) were in the range expected for the low hernatocrit we m e a s u r e d : i ~.9 + .,_..,on ;he second samples. M e a s u r e d acetone excretions were extremely variable and oi~en ~.,npn~s,,Jo~:~a~ v4th E.~,.~.~ < E~.h~~. This was surprising because the animarls were at ambient t e m p e r a t u r e so we did not expect c o n d e n s a t i o n problems with this very sohmle gas. All ~"Q distributions and subsequent analysis were d o n e with oniy live ga>,cs, i.,?. cx~Auding acetone. As explained in the Discussion, this d o e s not si~fific a n S v ~d-!'~c~ ~i3c r e s u l t s v,c reporL Figure I shows a ~>pical measured ~ " 0 dis,ribution. All o f ~.he distributions were ,a~im.~.,<.L4 witL c o n s i d c r a N e s h u n t , ~ s ) . T h e overall 9 / 0 ratio was high (2 to 7) because :~f c,m-:mu~;us ~rfificial ventik~d,an. Tabic 3 summarizes characteri'stics o f the V/Q d q f i b u t i o n s ~.,~-~ ~-a......~sr~ace ventilation (VD) exceeded . . ~ the • values estimated from a n a t o m i c p!us h>,trumcnt dead pace vok.m}e m e a s u r e m e n t s in all cases indicating i n t r a p u t m o n a r y . . . . .a ,coral " " i dead {;m?,l,,eo~,~,. . a,~ space. 0 s varied between animals but was quite reproducibk: ir~ 4 ei,~c~ ,q~imat There was a significant trend for 0 s to increase as (~-r ................... -. . . . . . . . . areas v.,.,e o b s e r v e d in six o f fifteen cases :{~':d ~,ni', ~ t ~ , casc: did they a c c o u r t abr mo, e than 5% o f 0 T . In all six cases the i~>a V () a,rc:,s > ere o.x-mauous w~th ..he shunt c o m p a r t m e n t on :he distribution (i.e. they

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m c m d e d the c o m p a r t m e n t with the lowest finite 9, Q,.Q. = 0.01) so it is difficult to be sure that they were not really shunt {see Discussion). The degree of Q/<) inhomogeneity exclusive o f shunt or <.,e~d ~'" space can be judged by the log standard deviation of the main m o d e blood flow distribution (log SDQ, table 3); this averages 0.47 _+ 0.9. Another measure of inhomogeneity is DISPR-E, which is 100 corrected for dead space (Gale et aL, t 9 8 5 ) . T h i s corresponds to an average arterialalveolar ,.~~-,-r m e r e n , ...~ , where the m a x i m u m is I00 so it can be thought o f a s a percentage !imitation. Because we observed such large shunts in the alligators, we also corrected R [or s h u n t : R':: = (R - [ 0 s / 0 r ] ) ~ ( 1 - [ 0 S ' 0 T ] ) . DISPR-~ averaged 4.56 ± 4.4 in the alligators (tabie 3). The residual sum of squares ( R S S ) betwee,a the measured and best ht da.~a was eeneratlv gooe hab~e 5). R a S was less than or equal to ~, m 8( <, o f the cases which is v
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compromised to obtain accurate data from the multiple inert gas elimination technique. For exampie, the overall ~'/Q was high because of continuous artificial ventilation. An anesthetized, artificially ventilated preparation was necessary to approximate steady state gas exchange which is assumed in the analysis. 1¢Io2 was similar to that of awake unrestrained alligators at room temperature (J. W. Hicks, personal communication) but it was certainly tess than that expected in awake alligators at the level of ventilation we studied. Hence, lung gas Po2 and Pco~ were nearer inspired tensions than in more physiological circumstances. The effects of this on potential local "v/Q matching by broncho- or vasoconstriction are unknown. The distribution of forces, and thereby air flow, probably differs with positive pressure versus spontaneous ventilation also. Hence, the V/Q distributions we measured must be considered representative of the intrinsic properties of this lung design when continuously ventilated at low metabolic rates. Note that although alligators me periodic breathers, the ventilatory rate we studied was similar to that during a ventilatory bout in awake alligators (Davies et al., 1982). Although ventilator rates we used were low by mammalian standards, in pilot studies we found no measurable effects of such low rates on inert gas data. Higher rates simply lowered lung 0 2 and CO 2 concentrations more. Any effects of such temporal '¢/(~ inequality must have been small and would show up 'as if' they were spatial inequality, which itself was small. Acetone data were not used to determine ;$'/Q distributions because in several cases acetone E was less than E of the less soluble gas diethyl ether; this is physiologically impossible according to the assumptions of the analysis~ Inert gas exchange with airway mucosa has been proposed as a mechanism of reduced acetone excretion (Zwart, 1983) and would represent such a violation of the assumptions. However, a model analysis of error free theoretical data, representative of that collected from our alligators, rhowed that the recovered ~'/0 distributions were not changed by omitting acetone data. Dead space changed less than 1 ~o and log SDQ increased less than 0.01 when theoretical data from unimodal or bimodal distributions were analyzed with all six gases versus the five gases without acetone. Shunt was not expected to change when acetone data were omitted (Rather and Wagner, 1982) and it did not. Similar results were also observed when comparing 5 and 6 gas analyses of experimental data sets that included normal acetone excretions (i.e. Eacetone > Eetb~r). Thus, our ~'/Q distributions may not distingtiish between trac dead space and very high ~'/0 exchange units but the effect on physiologic gas exchange is not significant.

;"/0_ distri&,tions. Althcagh we measured considerable shunt and dead space, the ~'¢'/(~ distributions ,,vere mostly unimodal and the log standard deviation of blood flow to the main mode averaged only 0.47 _+ 0.09. For comparison, this value obtained by the same methods is 0.90 + 0.46 in the unicameral Tegu lizard lungs (Hlasta!a et al., 1985), 0.56 + 0.30 in parabronchial duck lungs (Powell and Wagner, 1982) and in 95~o of normal humans it averages <0.4 (Wagner etal., t987). Hence, "V'/Q matching is relatively good in the multicamera! alligator lung except for shunting and dead space ventilation.

90

F,L POWELL AND A.T. GRAY

Low "V/(~regions were detected in six cases but they were all in low (i'Q compae~ments contiguous with the shunt compartment. Shunt was lower than av~:rage in these six cases (19~ 's 29~o) so the total blood flow to '~J/0 < 0.01 was similar in all cases. The ability to distinguish such small amounts of blood flow to very low ~,"/'Q ur~its from shunt is limited with our techniques (Ratner and Wagner, 1982) and we do not ascribe physiological significance to this distinction. The large shunt was the most striking feature of the V'/Q distributions. Central cardiovascular shunts are possible in the crocodilian heart but they are not expected in the conditions we studied (White, 1956, 1968, 1969). The right aortic arch leaves the left ventricle and is perfused by arterialized blood. The left systemic aortic arch leaves the right ventricle but it is also usually perfused by left ventricu!ar blood. Arterialized blood apparently reaches the left aortic arch via the foramen of i dzza which connects the two systemic arches. Cardiac cartilages and the balance of pulmonary and systemic vascular resistances prevent pressure gradients necessar.¢ to open the semilunar valves for direct right ventricular perfusion of the left aortic arch. This flow pattern is supported by pressure recording (White, 1968, 1969) and blood oxygen data (White, 1956). The only cases in which right to left shunting has been observed in ailigator~ are during apnea and these are reversed by artificial ventilation; anesthesia or hypoxia alone are not sufficient stimuli to cause the cholinergic pulmonary vasoconstriction that has been shown to cause right to left shunts (White, 1969). Hence~ we should not have central cardiovascular shunting in our preparation. Stronger evidence against central cardiovascular origins of the shunts we measured comes from several subsequent experiments in which arterialized blood was sampled from the left atrium; these experiments also showed similar large shunts (A. T. Gray, unpublished observations). We conclude that there was substantial pulmonary shunt in the alligators we studied. The anatomical basis for such shunts is unknown. Dead space recovered in the ~'/0 distributions (i.e. ~'/0 > 100) includes anatomic plus instrument dead space and intrapulmonary (analogous to flveolar) deed space. As discussed above, our resolution in this range is limited but the intrapulmonary dead space ventilation (i.e., inert gas (/D-anatomic VD-instrument "~/D) averaged 18.3 + 7.3~ of total ventilation. This is similar in magnitude to the animals' anatomic dead space which averaged 15 to 20~o of VT (unpublished observation). As discussed below, part of this alveolar dead space may be caused by molecular weight dependent gas phase diffusion limitations, however. The effect of this type of'~/0 inhomogeneity on steady state physiologic gas exchange can be predicted from fig. 2, which shows blood-gas partial pressure differences for gases with different partition coefficients, 2, given a typical alligator "v'/Q distribution. The distribution is corrected for instrument dead space so it is more representative of a normal alligator. For O2 and COz, 2 is near 1 and this is the region in which ~'/(~ mismatch has the largest effect on fig. 2. However, V/0 mismatch explains only a small part of the total arterial-mixed expired difference and the end capillary-arterial difference caused by shunt or ideal expired-mixed expired difference caused by dead space are much more important.

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Qualitatively, one can state that ~hunt w~_llaffect 02 more than C02, and vice versa for dead space, because 2co 2 > 2o,. However, using fig. 2 to quantitatively determw, e whetlaer shunt or dead space is more important for O2 and CO2 requires more exact data for these gases. Specifically, such determinations require the effective conductance rados for the gases: (V/2Q)efr = (VE[i - VD/VT])/(2QT[1 - Qs/~tx]). For awake alligators at 25 °C, (V/2Q)aris estimated as 1 to 3 for 02 (J. W. Hicks, personal communication). In that case, shunt effects on Oz are less than dead space effects on CO 2 (fig. 2). We measured arterial blood gases in a few experiments and they were very different from values in the let't atrium of awake alligators (J .W. Hicks, personal communication); Po2 in our experiments was low (ca. 50 vs 100 Torr) and Pco2 was also low (ca. 15 vs 28 Tow). This is consistent with the large shunt and high overall '¢/(~ in our experiments and suggests that such pulmonary shunts may not occur in some natural conditions. More studies of gas exchange in awake unrestrained animals wil! be required to determi-,e the quantitative role of the different limitations in nature. Molecular weight-dependent limitations. We observed inert gas retention data that was consistent with a molecular weight-dependent limitation. One test for such a limitation is comparing the difference in retentions of heav2¢ and light molecular weight inert gases of the same solubility (Piiper and Scheid, 1987). Inert gas elimination is not significantly limited by membrane diffusion and if solubilities are identical then the effects of V/(~

92

F.L. POWELL A N D '~..T. GRAY

i~lhomogeneity are identical. Thus, increased retention of a heavier gas could indicate a molecular weight-dependent limitation like stratification. Downs and Wagner (1983) showed that stratification, as modeled by Scheid (1981), should also systematically and predictably affect the retentions of different molecular weight gases with dh"ferent solubilities. Stratification increases the residual error between measured R and the R predicted for the ~,'/Q distributions recovered assm-ning no diffusion lixnitations. Stratification increases the overall error in fit to the data, RSS, mainly because the difference in residual errors of fit to the heavy gas enflurane (eenfl) becomes more positive while that for the lighter gas cyclopropane (ecyo~o)becomes more negative. Experimental error should result in both ee,~n and ~cycloaveraging zero. We observed pos!tive (eenn - ~cydo) in every data set and the average was significantly greater than zero which is not consistent with the assumption of gas phase diaffusion equilibrium. Hlastala etal. (1981) proposed minimizing the error in fit to multiple inert gas elimination data as a means of estimating stratification diffusior~ resistances. Because our overall fit to data by the model assuming no stratification (i.e. RSS) was withha the limits of experimental error, we could not use this as a criterion. However, we were able to use their approach by minimizing (ee,n - ecy~o). As presented in the Results, our best estimate of D~tra t in the alligator preparation we studied is 6/~mol/(min. Torr._~:g). However, we emphasize that this is only an estimate and that if the model assumption~ are not valid, for example, because there are important convective-diffusive interactions (Engel, 1985), then our estimate may be in error. Compared to alveolar lungs (normalizing for body mass), the alligator has a much greater molecular weight dependent limitation. Dstra t estimated by the same methods for rats (Hlastala et aL, 1981) is approximately seven-fold greater. Estimates of diffusive mixing conductances in man (Piiper and Scheid, ~°Q'7~ ,,,,, j -,'e at least ten-fold greater man our estimate of D s t r a t in alligators. This could be qualitatively predicted from the larger air spaces in the alligator compared to alveolar lungs. Quantitative predictions from lung morphornetry would be tent~ous, however, considering the simplicity of the models used for analysis and their many untested assumptions. Compared to other diffusion limitations, D~t~ ~estimated for alligators approximately equals morphometric estimates of membiane Do2 in crocodiles (Perry, 1988) and is ten-fold greater than rebreathing DLco in alligators (Gray, unpublished observations). In humans, D s t r a t is not even 20 ~o of morphometric membrane Do~ (Weibel, 1984) and only two-fold greater than rebreathing DLco (Meyer et al., 1981). Hence, gas phase diffusion limitations constitute a smaller fraction of total diffusive resistances in alligators than in humans but this is because the membrane diffusion resistances are comparatively large in alligators. The physiologic significance of gas phase diffusion limitations is that they impair intrapulmonary gas mixing and can increase physiologic dead space (Piiper and Scheid, 1987). Hlastala et al. (1981) found that neglecting stratification in the analysis of inert gas data for "v'/(~ distributions in rats could increase dead space from 17 to 39~o of'V'E. Downs and Wagner (1983) predicted similar increases in physiologic dead space if the

ALLIGATOR "¢/()

93

levels of stratification we found in alligators are neglected in the analysis. Thus, some of the intrapulmonary dead space we measured (see above) may actually be ineffective diffusive mixing in the alligator lung instead of unperfused exchange units in the lung. In summary, the molecular weight dependent limitation we estimated in this multicameral reptilian lung is small compared to other limitations from membrane diffusion, shunt and dead space. The effects of'~/0 mismatch in perfused and ventilated lung units were also small. This suggests that gas phase diffusion and V / 0 matching may not be primary selective pressure points for the evolution of more complex lungs.

Acknowledgements. We gratefully acknowledge the advice of Drs. Fred White and James Hicks, the technical assistance of Leslie Byron and Donald Ward and the skills of Carrie Wagner in preparing this manuscript. We especially thank Ted Joanen, Larry McNease, Ruth Elsey and the staff at the Rockefeller Wildlife Refuge for their assistance with the alligators.

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Pox~ell, F. L. and P. D. Wagner (1982). Measurement of continuous distributiot~s of ventilation-perfusion in non-alveolar lungs. Respir. Physiol. 48: 219-232. Powell, F.L. and P. Scheid (1989). Physiology of gas exchange in the a~!an lung. In: Form and Function in Birds. Vol. 4, edited by A.S. King and J. McLel!and. London, AcJdemic Press. Ratner, E.D. and P.D. Wagner (1982). Resolution of the multiple inert gas method for estimativ.g ~1A/Q maldistribution. Respir. P,~ysiol. 49: 2o3-313. Scheid, P., M.P. Hlastala and J. Piiper (1981). Inert gas elimination from lungs with stratified inhomogeneity: theory. Respir. Physiol. 44: 299-309. Wagner, P.D., H.A. Saltzman and J.B. West (1974a). Measurement of continuous distributions of ventilation-perfusion ratios: theory. J. Appl. Physiol. 36: 588-599. Wagner, P.D., P. F. Nauman and R. B. Laravuso (1974b). Simultaneous measurement of eight foreign gases in blood by gas chromatography. J. AppL Physiol. 36: 600-605. Wagner, P.D. and F.A. Lopez (1984). Gas chromatography techniques m respiratory physiology. In: Techniques in the Life Sciences, P4/I, Respiratory Physiology~ P403, edited by A. B. Otis. County Clare, Ireland, Elsevier Scientific Publishers Ireland Ltd., pp. 1-24. Wagner, P.D., G. Hedenstierna and G. Bylin (1987). Ventilation-perfusion inequ:lity in chro~,ic asthma. Am. Rev. Respir. Dis. 136: 605-612. Weibel, E.R. (1984). The Pathway for Oxygen: Structure and function in the Mammall,r~ Respiratory System. Cambridge, Massachusetts and London, Harvard University kress. White, F.N. (1956). Circulation in the reptilian heart (C~irnan sclerops). Anat. Rec. 125: 417-431. White, F..N. (1968). Functional anatomy of the heart of reptiles. Am. Zool. 8: 211-219. White, F.N. (1969). Redistribution of cardiac output in the diving alligator. Copeia 3: 567-570. Young, I. H. and P. D. Wagner (1979). Effect ofintrapulmonary hematocrit maldistribut:.on on 0 2, CO~ and inert gas exchange. J. Appl. PhysioL 46:240-248