Acta Anaesthesiol &and 1989: 33, Supplementum 90: 22-27

Pulmonary gas exchange in panting dogs: a model for high frequency ventilation MICHAEL MEYER, GUNTER HAHN and JOHANNES PIIPER Department of Physiology, Max Planck Institute for Experimental Medicine, Gottingen, FRG

Panting in animals can be expected to represent a naturally occurring physiological counterpart to today’s techniques of mechanical high-frequency ventilation. To analyze the mechanisms underlying the gas exchange inefficiency during ventilation with high frequencies, steady-state pulmonary gas exchange was studied in seven conscious dogs (32 kg mean body weight) during panting elicited by mild thermal stress. The animals had a chronic tracheostomy and an exteriorized carotid artery loop and were exposed to 27.5”C ambient temperature for 2 h (65% relative humidity). Open-circuit techniques were used and Po? and Pco? from the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-bold phase- locked gas sampling technique. POP and PCOZ were determined in arterial blood collected from the carotid artery. During the exposure, the following variables of steady-state gas exchange were determined (means? SD): breathing frequency 313 19 min-1; tidal volume, 167 21 ml; total ventilation, 52 f 9 1’ min-I; effective alveolar ventilation, 5.5 1.3 1. min-’; partial pressures (torr; a, arterial; E’, end-tidal): Pao?, 106.2 i 5.9; Pacor, 27.2 k 3.9; (PE’-Pa)o?, 26.0 5.3; (Pa-PE’)col, 14.9 k 2.5. According to the conven- tional lung model, parallel-dead space ventilation (ventilation of unperfused lung regions) would account for about 55% of the alveolar ventilation and for 3 of the (PE’-Pa)oz difference. However, the lack of an ‘alveolar plateau’ in the COP and 02 expirograms suggests that incomplete serial mixing in peripheral airways contributes to the enhanced gas exchange inefficiency during panting as reflected in the increased blood/gas differences for 0 2 and GO?.

Key words: Alveolar gas exchange; arterial blood gases; dog; heat stress; high frequency ventilation; panting.

High-frequency low-tidal volume ventilation (HFV) has been shown to maintain adequate gas exchange in experimental animals and man. Similarly, animals panting to produce thermoregulatory evaporative heat loss exhibit high-frequency low-tidal volume breathing, which may be considered to represent a naturally occurring physiological counterpart to to- day’s techniques of mechanical high-frequency venti- lation. The frequency of breathing in panting dogs has been shown to be close to the resonant frequency of the respiratory system, about 300.min-’ or 5 Hz (1, 2). Panting at resonant frequency may be expected to represent the best compromise to satisfy the several demands placed on the respiratory system, e.g. gas exchange, heat exchange, and mechanical efficiency. The increase in ventilation that is associated with pan- ting not only favors evaporative water loss but would also affect arterial blood gases and acid-base balance, leading to a hypocapnic alkalosis. This effect is par- tially offset by the fact that the tidal volume is de- creased and the increased ventilation is largely restric- ted to dead space.

The aim of the present study was to investigate steady-state gas exchange and the efficiency of intra- pulmonary gas mixing in panting dogs subjected to

mild thermal stress. Advanced techniques for the analysis of alveolar gas exchange were used and the experimental approach is intended as a model for high-frequency mechanical ventilation to complement our previous studies of HFV in dogs (3, 4).

MATERIAL AND METHODS Seven healthy mongrel dogs (32 kg mean body weight) surgically prepared with a chronic tracheostomy and an exteriorized carotid artery loop were studied. They were trained to rest quietly in the prone or lateral decubitus position while the laboratory ambient temperature was raised from about 22 to 27.5% for about 2 h (mean relative humidity 65%).

Experimental set-up Open-circuit methods were used and measurements of the respiratory gases, OZ and COZ, were performed by mass spectrometry and blood gas electrodes. A cuffed cannula was inserted into the tracheostomy and connected to a two-way non-rebreathing valve interfaced by an in-line respiratory phase-lock gas sampling device. Thr sampling system was designed to overcome the limitations imposed by the response characteristics of the mass spectrometer for continuous monitoring of respiratory gas composition a t very high breathing frequencies. The principle of operation is by discontinuous gas coller- tion of a small volume fraction from the main gas stream at any selected point of the respiratory cycle (Fig. 1 ) . Thr gas sample is temporarily trapped in a small mixing chamber which is connerted to

PULMONARY GAS EXCHANGE IN PANTING DOGS 23 the main breathing line and maintained a t subatmospheric pressure (about 600 torr) by a vacuum pump and a variable flow resistance. Sample input to the mixing chamber results from the pressure differ- ence and is controlled by a miniature ultra-speed piezoelectric valve. Periodic repetition of this procedure on each breathing cycle yields identical composition of gas in the mixing chamber and the main respiratory gas flow at the point of sampling. The mixing chamber thus functionally serves as a sample-hold capacitance. In steady- state, gas concentrations in the mixing chamber will be constant and will be available for a gas analyzer whose response characteristics may bc too slow for direct monitoring in the main gas stream. The sample-hdd principle of gas sampling may be used in two distinct modes. In phase-locked mode (Fig. 1, right panel), sampling is locked onto a selected point of the respiratory cycle, e.g. end-tidal, and is synchronws with breathing frequency. In scanning mode, sampling is asynchronous to breathing frequency and the point of sampling is advanced by infinitesimal increments over the entire cycle (infinitesi- mal moving frame). The concentration profile that is recorded from the mixing chamber thus constitutes the gas concentration profile of the breathing cycle which would otherwise be obtained by envelope averaging of an equivalent number of continuous scans. A detailed account of the sampling system which was specially designed for application at very high breathing rates (3-30 Hz) is given elsewhere

End-tidal gas was collected by the sampling unit and analyzed for fractional concentration (FE’) of 0 2 CO? and N2 by a modified Varian M3 mass spectrometer (cf. 6). Similarly, inspired gas compo- sition (FI) was determined by shifting the point of sampling to the inspired part of the respiratory cycle. Mixed-expired gas, collected in a 7-liter spirometer (FE), and calibration gas mixtures were di- rected to a second sampling line of the sampling unit. Remote- controlled changeover between the two sampling lines facilitated determination of FE’, FE, and FI with interpolated calibration while the device was in place a t the animal’s airway opening. End-tidal concentrations of 0 2 and CO2 were converted into partial pressures, assuming full water vapor saturation at the arterial temperature measured in the carotid artery by a miniature thermistor probe.

Arterial blood samples were obtained from a Teflon catheter insert- ed percutaneously into the exteriorized carotid artery. The samples were collected anaerobically in 170 pI heparinized glass capillaries

(5).

Voriabble tlow

* Vacuum pump 1 1

by a miniature automatic blood sampling system which enabled catheter and tubing to be flushed with saline solution after blood sampling without disturbing the animal.

Experimental protocol This study was designed to assess pulmonary gas exchange function during mild thermal load in sleadystute conditions of gas exchange in conscious dogs. T h e level of arousal and the animal’s responsive- ness to environmental stimuli, however, renders steady-state con- ditions for a sufficient period of time difficult to achieve. To obtain enough measurements within about 2 h of heat exposure, the dogs received a mild tranquilizer (0.1 mg/kg acepromazin-maleat, 0.08-0.24 mg/kg droperidol, i.m.) which had negligible effects on their respiratory behaviour, but made them less susceptible to en- vironmental stimuli.

Five steady-state measuring periods were completed in a given session. In each period, four arterial samples were obtained over 2 min bracketing the collection of mixed-expired gas. The end-tidal- arterial differences, (PE’-Pa)oz and (Pa-PE‘)col, were calculated from the mean value of the 4 arterial blood samples and the end-tidal values averaged over the corresponding sampling period.

Analysis of alveolar gas exchange Volumes, ventilations, and gas exchange rates were calculated ac- cording to established relationships for open-circuit breathing. The ratio of series (or anatomic) dead space ventilation (VDS) to total ventilation (VE) was obtained from the Bohr equation:

The effective (or physiological) dead space ventilation (VD,,,) was obtained by replacing PE’CO~ by Pacoz in Eq. ( 1 ) . The effective alveolar ventilation ( %‘A~~Y, representing ventilation of blood-perfused lung regions) results from the difference between the total ventilation and the effective dead space ventilation ( V A , ~ = VE - OD,,).

The ratio of parallel (or alveolar) dead space ventilation (VDP, representing ventilation of poorly-perfused or unperfused alveolar regions) to alveolar ventilation (VA = VE-VDS) is calculated from the relationship:

Gas concentration

A* 1 I I I

I

I Flow I

I I I ’ -.lL 1, [Sampling time1 1 I I

I I +-aOmsec+ f ‘ = ~ s e c - ’ m r n s e c

r t d - 1 I - I I 1 I I

Tlme - 1-e Trigger Zero -flow

2 I talitxation - gas mixture

Fig. 1. Experimental set-up (left) and principle of phase-locked end-tidal gas sampling (right).

M. MEYER ET AL.

0.02

Fco, 001

24

- -

- -

For a quantitative analysis of the components underlying the blood/ gas differences of 0 2 and COP, the 'ideal alveolar' air approach based on the classic 3-compartment model of Riley & Cournand (7) was employed, The ideal alveolar POZ, PAIO?, was obtained as:

(3) (Pa - PI)COZ

m PAiOz = h O ? -

where m is the slope of the gas-R-lines of the CO2-02 diagram:

(PB-PI)Coz (PI - PB)OZ

m = (4)

RESULTS All dogs consistently chose a respiratory pattern of very rapid shallow breathing at frequencies of about 300. min-' as a result of mild thermal stress by acute exposure to 27.5"C for 2 h. The increase in breathing rate followed a rapid initial switch to about 200 * min-' and asymptotically approached a steady level at the indicated breathing frequency. The arterial blood tem- perature was unchanged during the thermal challenge (mean value SD: 38.6 O.S0C), indicating that the normal heat production continued to be effectively dissipated at the elevated ambient temperature.

A typical measurement of steady-state gas exchange in a conscious unrestrained panting dog is shown in Fig. 2. The record displays continuous monitoring by phase-locked sampling of end-tidal gas fractions ( FOZ and Fco~) along with an analog equivalent of cycle time (t). The mean cycle time is about 180 ms corre- sponding to 5.5 Hz breathing frequency.

The results (mean values & SD) of steady-state measurements of respiration and arterial blood gases following exposure to 27.5"C are compiled in Table 1 (left column, 'panting'). For comparison, previous data from our laboratory (cf. 8) on anesthetized dogs

breathing spontaneously through an endotracheal tube at normal room temperature, have been included (right column, 'control'). The following important dif- ferences become apparent when panting is compared with normal breathing.

(1) Breathing frequency ( f ) , total ventilation (VE), alveolar ventilation ($'A) and effective alveolar venti- lation ($'A~,T) were increased while tidal volume (VT) was decreased.

(2) Effective (physiological) dead space ventilation (OD,,), series ( ~ D s ) and parallel ( ~ D P ) dead space ventilations were increased in relation to total venti- lation (VE) or alveolar ventilation (VA) , respectively.

(3) In arterial blood, Po2 was increased and P C O ~ lowered but there was only a slight hypocapnic alkalo- sis. The extent of the alkalosis during panting is re- duced by the fact that tidal volume is decreased and the increased total ventilation is largely restricted to dead space.

(4) The pronounced increase of parallel (alveolar) dead space ventilation (VDP) suggests that more than 50% of the alveolar ventilation constituted ventilation of poorly perfused or unperfiused lung regions. The effect of alveolar dead space ventilation is reflected in the sizable arterial-to-endtidal PCOZ difference, about 15 torr. If the blood/gas difference for COZ is attributed to alveolar dead space ventilation, the ( PE'-PA~)o~ component (about 17 torr) which is mainly deter- mined by the same mechanism would account for '/1 of the total (PE'-Pa)o* difference.

Table 1 Ventilation and gas exchange in panting and in normally breathing dogs.

Panting Control

Room temperature ("C) 27.5 f 0.7 22.0 Arterial temperature ("C) 38.6 f 0.6 37.4 0 2 uptake (ml sTpD.min-I) 193f37 170 CO? output (ml sTpD.min-') 168f33 146 Exchange ratio, R (-) 0.88 f 0.06 0.86 Resp. frequency, f (min-I) 313219 11.6 Tidal volume, VT (ml BTPS) 167f21 488 Total ventilation, VE (1 BTPS' min-') 52 f 9 5.7 Alveolar ventilation, VA (I BTPS . min-1) 1 2 + 3 3.9 Effec. ah . ventil., V A , ~ (I ~ ~ p s . m i n - l ) 5.5 f 1.3 2.9 Arterial pH (-) 7.45k0.03 -

Arterial PCOZ, Paco? (torr) 27.2 f 3.9 41.2 Arterial Po?, Paoz (torr) 106.2 f 5.9 81.3 (Pa-PE') CO? (torr) 14.9f 2.5 5.4 (PE'-Pa)oz (tom) 26.0 i 5.3 24.3 (PArPa)o* (torr) 9.Of 2.4 17.5 ( PE'-PAI)o? (torr) 17.3 f 3.5 6.8 VDS~VE (3 0.77 f 0.02 0.31 VDP/VA (-1 0.54 f 0.04 0.13 VD&'E (-) 0.90 f 0.02 0.40

25 PULMONARY GAS EXCHANGE IN PANTING DOGS

DISCUSSION Breathing pattern The pattern of panting upon exposure to mild thermal stress was that of rapidly increasing breathing fre- quency and decreasing tidal volume approaching a steady breathing rate at about 2 3 0 0 . min-I. Similar findings have previously been reported by Hemingway (9) and Crawford (1) who showed that dogs were panting at the resonant frequency of the respiratory system determined at 5.3 Hz. In the present series, all dogs consistently switched to panting frequencies ranging from 5.1 to 5.6 Hz and this uniform response was preserved when the same individuals were studied on several occasions with test-free intervals of 2 to 3 months. The dogs apparently took advantage of the natural rebound of the respiratory system to minimize the extra energy expenditure of panting, which, if the dogs were to pant at any other frequency, would be quite large. The 0 2 uptake, about 6 ml.kg-l.min-I, during panting was comparable to that in anesthetized spontaneously breathing normothermic dogs.

Differences become apparent when the present data are compared with the study of Maskrey & Jennings (1 0) which was similar in design to ours. Their dogs, when subjected to 30°C ambient temperature were panting at a mean frequency of 1 9 4 . r n k 1 (3.2 Hz) but the inter-individual variability of the animals' re- sponse to heat stress was large. The inhomogeneity of the group is also apparent from the considerable variability of the oxygen uptake, the overall mean value being twice as high as in the present study. Apart from differences in the respiratory behavior, the low gas exchange ratio, 0.54 during 2 h exposure or 0.39 during 48 h exposure suggests that the dogs of Ma- skrey & Jennings (10) were not in steady state. For the present series, the gas exchange ratio (0.88, cf. Table 1 ) indicates that the measurements were per- formed in proper steady-state conditions of gas ex- change.

Functional inhomogeneity of lungs during panting In the classic model of Riley & Cournand (7) complete mixing within parallel lung compartments and ab- sence of diffusion limitation across the alveolar-capil- lary membrane is inherently assumed. Hence, all of the inhomogeneity giving rise to alveolar-arterial dif- ferences is attributed to unequal distribution of al- veolar ventilation to perfusion. On these grounds, the distribution of ventilation to the parallel compart- ments as derived from measurements during normal breathing and during panting is presented in Fig. 3 (upper panel, parallel model).

During panting the fractional series dead space ven-

Normal breathing Panting

1.m 1M

Parallel model

as0 010

Fig. 3. Schematic representation of mechanisms of functional inho- mogeneity and blood/gas differences during normal breathing and panting according to parallel (upper panel) and serial (lower panel) lung model.

tilation, VDSIVE, is increased in panting by a factor of 2.5, from 0.31 to 0.77. Since the absolute values for series dead space (VDS = ( V D S / v E ) . V E / ~ ) were similar in both conditions, the increased series dead space ventilation must have been mainly due to the in- creased respiratory frequency.

The increase of the fractional parallel dead space ventilation, f i D P / v A , from 0.13 to 0.54, would suggest that a major portion of the alveolar ventilation is redistributed to the unperfused compartment, or part of the perfused compartment is deprived of its blood flow.

The fraction of the total ventilation ventilating the blood-perfused compartment, VA,F~~VE ( = 1 - frD,r/

VE), is diminished from 0.60 to 0.10. Nonetheless, the effective alveolar ventilation, VA~E, is increased during panting leading to hypocapnic alkalosis (pH = 7.45).

However, straightforward application of the paral- lel-compartment model to conditions of high-fre- quency breathing is questionable mainly for the fol- lowing reasons. During normal breathing, the expiro- gram (plot of gas concentration versus expired volume) of 0 2 and COZ generally exhibits a sloping alveolar plateau. The steady change of gas concen- tration in the later course of expiration is interpreted to reflect sequential emptying of alveolar compart- ments with differing Pcop and Po:, (due to ValQdistri- bution), the poorly ventilated compartment with high- er Pco2 and lower Pop expiring late. By contrast, the expirogram of 0, and CO2 obtained in a panting dog (Fig. 4; for recording technique of the expirogram during panting see ref. 5) completely lacks an alveolar plateau and appears to be terminate in the middle of the steep portion that conventionally marks the transition of series dead space into the alveolar space.

26 M. MEYE

e EX P :: INSP- -

-

-

-

0.03 -

.‘, c02

0.02 -

j 02 001 -

0.21

0.20

Fo*

0.19

0.18

0 b 4 0.17 0 x)O 200 Joo

Expired volume lmll

Fig. 4. Gas concentration profiles of CO1 and 0 2 during panting.

If, however, sequential emptying of unperfused and perfused parallel compartments were the only mech- anism of functional inhomogeneity, that would ac- count for a steep slope of the expirogram, no positive (Pa-PE’)coZ difference would be expected to occur.

I t is therefore of interest to consider an alternative model, such as the serial trumpet-shaped model de- picted in Fig. 3 (lower panel). In this model, the end- expired value can be interpreted to reflect the partial pressure a t a certain volumetric depth which, during normal breathing may be located in the alveolar space, but with shallow low-tidal volume panting would orig- inate in the more proximal ‘transitional’ region. Straightforward application of this model suggests that the (Pa-PE’)coy difference is due to series or stratified inhomogeneity, i.e. to an axial or longitudinal PCO? gradient.

The presence of series inhomogeneity has been dem- onstrated by differences of washout kinetics of two inert gases with widely differing diffusivities (He and SFb) in anesthetized mechanically ventilated dogs but its limiting effect on gas transport during normal breathing is expected to be small (1 1). However, the role of incomplete gas mixing may be expected to be enhanced during high-rate shallow breathing. Prelimi- nary results from simultaneous washout of He and SFc during panting have revealed diffusion-dependent differences of washout kinetics of the two gases (cf. 3), suggesting that gas phase diffusion limitation contri- butes to the gas exchange inefficiency that is reflected in the increased (Pa-PE’) co2 and ( PE’-PA;)O~ differ- ence during panting.

Parallel and series inhomogeneity may occur in close association. The distinction and separation of their effects which are qualitatively similar, ultimately

5R ET AL.

decreasing the efficiency of alveolar gas exchange, may be difficult if not impossible. Thus, during panting there may simultaneously exist some alveolar dead space expiring early contributing to the steep slope of the C02 and O2 expirograms and incomplete serial mixing in peripheral airways, producing the large (Pa- -PE’) coz difference.

Panting us. high-jrequency ventilation The present study has demonstrated that in dogs pan- ting at about 5 Hz breathing frequency, the tidal volume always exceeds the anatomic dead space ( V D S ~ VT = 0.77). When compared to current techniques of mechanical high-frequency ventilation, panting in dogs may resemble conditions encountered in high- frequency jet ventilation or low-frequency oscillatory ventilation. I t is in contrast with high-frequency oscil- lation, where tidal volumes smaller than the dead space have been shown to provide adequate gas ex- change. Alveolar-arterial Po? and Pco2 differences dur- ing high-frequency oscillation have been determined in anesthetized dogs with 10 to 40 Hz oscillations but were found to be smaller compared with the present series (4). In particular, the Pco? difference was practi- cally zero. In these experiments the end-tidal values were obtained by rapid and deep active expiration by the ventilator (after interruption of high-frequency oscillation) and therefore are not directly comparable to the end-tidal values determined in the awake dogs of the present series. The ventilation efficiency, ex- pressed as the ratio of effective alveolar ventilation to total ventilation, was in the range of 3 to 12% during high-frequency oscillation (piston tidal volume 20-40 ml, frequency 10-40 Hz, cf. Ref. 4). The values are thus comparable with the mean value of the present study ( { ~ - ~ D , , / V E } * ~ O O ) , 1 lob, which is in similar range.

CONCLUSIONS Dogs exposed to acute mild heat stress (27.5”C) con- sistently exhibited steady shallow panting at frequen- cies corresponding to the resonant frequency of the respiratory system. During panting at about 5 Hz frequency, tidal volume always exceeded the anatomic dead space. The reduction of the efficiency of gas exchange as reflected in the considerable blood/gas differences for 0 2 (26 torr) and CO:, (15 torr) can be attributed to increased fractional series and parallel dead space ventilation (according to parallel-compart- ment lung model) and to incomplete intrapulmonary gas mixing (stratification, according to serial distrib- uted trumpet-shaped model). The ventilation ef-

PULMONARY GAS EXCHANGE IN PANTING DOGS 27

ficiency of high-frequency similar in both conditions.

oscillation and panting is

ACKNOWLEDGEMENTS Supported by the Deutsche Forschungsgemeinschaft, SFB 330, Got- tingen.

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Address: Prof. Dr. med. Michael Meyer Department of Physiology Max Planck Institute for Experimental Medicine Hermann-Rein-Str. 3 D-3400 Gottingen FRG