Variations in pulmonary gas exchange due to changes in pulmonary artery pressure and flow

JOURNAL

OF SURGICAL

RESEARCH

18,

431-435 (1975)

Variations in Pulmonary Gas Exchange Due to Changes in Pulmonary Artery Pressure and Flow MICHAEL

E. MINER, M.D. AND NORBERTO C. GONZALEZ,

M.D.

The Department of Surgery, See tion of Neurological Surgery, and Department of Physiology, The University of Kansas Medical Center College of Health Sciences and Hospital, Kansas City, Kansas 66103 Submitted for publication December 11, 1974

Effective gas exchange in the lung is achieved by an adequate matching of ventilation to perfusion. In a normal, erect lung, the distribution of ventilation and perfusion is such that several alveolar-capillary units can be observed. At the apex of the lung, alveoli that are hyperventilated with respect to their perfusion can be found. These alveolar-capillary units contribute to an arterial-alveolar Pco, difference, and their magnitude can be assessedby a calculation of the alveolar dead space to alveolar tidal volume ratio. At the bottom of the erect lung, alveoli that are hyperperfused with respect to their ventilation are present, and they contribute to decrease the arterial oxygen tension, and to generate an alveolararterial PO2 gradient. Their magnitude can be calculated by the venous admixture, or shunt equation. Anatomical arteriovenous shunts in the pulmonary circulation will affect gas exchange in the same manner. The largest bulk of the alveolar-capillary units show a ventilation that is commensurate with their perfusion. There can be another possible combination of ventilation-to-perfusion relationships, i.e., units with neither ventilation nor perfusion. They would not contribute to either the alveolar dead space to alveolar tidal volume ration, or the venous admixture, and the lung functions as though these units were not present. The effect of alterations in the ventilationto-perfusion relationship upon pulmonary gas exchange have been studied theoretically [9, 17, 181, in experimental animals [7, 13, 15, 23, 25, 281, and in patients [ 1, 3, 4, 8, 12,

16, 191.Less is known, however, concerning the effects of passive hemodynamic changes in the pulmonary circulation upon gas exchange. In previous experiments, we observed a positive, linear relationship between cardiac output and venous admixture in animals under controlled ventilation [7]. In order to provide additional information concerning the specific influence of passive hemodynamic alterations upon pulmonary gas exchange, a series of experiments were performed on isolated, perfused dog lungs. METHODS Mongrel dogs (20-25 kg) were anesthetized with Na pentobarbital (30 mg/kg iv), and placed on a Harvard respirator, after a tracheostomy had been performed. Approximately 400 ml of blood was initially obtained from each animal. That blood and 200 ml of dextran was used to prime the perfusion circuit. Through a midline thoracotomy incision, the chest was opened and a cannula placed in the left atrium. The dogs were then exsanguinated, and the blood, plus half of its volume in dextran, were mixed together, and added to the perfusion circuit. The right main-stem bronchus was ligated, the pulmonary artery cannulated, and the lung removed from the animal. The lung was suspended in the upright position and the perfusion begun. The time elapsed between death and the initiation of perfusion was no longer than 20 min. Ventilation was maintained on room air and rebreathing prevented by a one-way valve interposed into the system. End expira-

431 Copyright n 1975by Academic Press, Inc. All rights of reproduction in any form reserved.

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tory pressure could be adjusted by increasing the resistance to expiration. The perfusion circuit consisted of a stainlesssteel disc oxygenator in which the blood was equilibrated with gas mixtures. The composition of the gas mixtures was determined by gas flowmeters from an anesthesia machine. A heat exchanger, a roller pump, a damping apparatus to maintain nonpulsatile flow, and a filter, led to the pulmonary artery. From the lung, a mobile reservoir was interposed between the left atrium and the disc oxygenator. Sampling catheters were present in the tracheal tube, pulmonary artery, and left atrium, such that gas and blood could be obtained for analysis, as well as pressures recorded, and left atria1 temperature measured. An electromagnetic flowmeter constantly monitored flow through the pulmonary artery. The end expiratory pressure was maintained at approximately 5 cm of water. The base of the lung was taken as zero reference level for blood pressures. Mixed expired gases were collected and analyzed from an aluminum bag, and end tidal Co, concentration was continuously monitored. Both the pulmonary arterial PC,, and PC,, were maintained at approximately 45 mm Hg. The preparation proved to be stable for 23 hr, and its efficiency as a gas exchanger was satisfactory. While breathing room air, arterial Pco, and Pa2 values were approximately 95 and 30 mm Hg, respectively. The alveolar dead space ratio (alveolar dead space to alveolar tidal volume ratio) was calculated: Anatomical Dead Space =

F *co2 - FEco 2 x v, F*co2

Physiological Dead Space =

P TO2

- ‘Eco P ko2

2 x v,

Alveolar Dead SpaceRatio

F

= fractional concentration of CO2 in the alveolar air. The last portion of expired air was assumed to represent alveolar air. F EC02 = fractional concentration of CO, in the mixed expired air. P%02 = partial pressure of CO2 in the arterial blood. P Eco2= partial pressure of CO2 in the mixed expired air. = Tidal Volume VT *co2

The venous admixture (shunt) was calculated: Shunt = End Cap. 0, Content End Cap. 0, Content Left Atria1 0, Content Pulmonary Artery O2 Content The oxygen content was calculated from measured PO2 and Hb concentration. The Severinghaus nomogram [23] was used to calculate 0, saturation of hemoglobin. Appropriate corrections were used for temperature. Twenty-eight dogs were divided into three groups and examined in the following manner: Group I. The flow was maintained constant while the left atria1 pressure (LAP was elevated. This resulted in an increase in the pulmonary artery pressure (PAP). Group ZZ. The LAP was maintained at zero, while flow was increased. PAP increased to comparable levels as in Group I. Group ZZZ. Pap was maintained essentially constant by initially having the flow low and the LAP elevated, then simultaneously increasing the flow and reducing the LAP.

MINER AND GONZALEZ:

VARIATIONS

IN PULMONARY

GAS EXCHANGE

Tn ALV. 8

8

41.023.2

23.2 2 3.0

8.42 Ix)

5.9 +,0.9

FIG. 1. The effect of elevating left atria1 pressure at constant flow. ALV ID/IT = Alveolar Dead Space Ratio expressed as percent. QS/QT = Venous Admixture expressed as percent. All pressures expressed in cm of water, and flow as ml per minute. Q = 292 f 5 ml/ min; EEP = 4.4 f 0.3 cm H,O, n = 8.

T

TA

292+49

7 15f45

AL’/%

23.2k3.0

299+3.1

!.?I

5.9kO.9

22.e3.8

FLOW

433

Fig. 3. The effect of maintaining pulmonary artery pressure constant while simultaneously altering left atria1 pressure flow. See Fig. 1. EEP = 4.3 cm H,O; n = 10.

lowered to zero and the flow increased to 7 15 RESULTS ml per minute, thereby maintaining PAP Group I. The effect of elevating LAP constant. The alveolar dead space ratio did from 0 to 25 cm of water, at a constant flow not change significantly, but the venous of 292 ml/min, resulted in the PAP inadmixture increased from 5.9 to 22.0% creasing from 24.5 to 32.7 cm of water (Fig. 1). The alveolar dead space ratio decreased (Fig. 3). from 41 to 23.2%, and the venous admixture DISCUSSION decreasedfrom 8.4 to 5.9%. Passive hemodynamic interventions affect Group ZZ. The PAP was increased from gas exchange in the lung, and these effects 25.8 to 32.9 cm of water, by increasing the can be quantitated by measuring the alveolar flow from 293 to 715 ml per minute. LAP dead space ratio and venous admixture. PAP was held at zero. The alveolar dead space and the alveolar dead space ratio were inratio decreased from 45% to 30%. However, versely related, and the effect of changes in the venous admixture increased from 12% to the PAP on the alveolar dead space ratio are 22% (Fig. 2). independent of the mechanisms by which the Group ZZZ. The PAP was maintained PAP is changed. In Groups I and II, the constant at 32.5 cm of water. Initially, the PAP was elevated to comparable levels by LAP was 25 cm of water and the flow 292 ml two separate mechanisms, but the alveolar per minute. Simultaneously, the LAP was dead space ratios were not significantly different. This is further illustrated in the experiments of Group III, where PAP was kept constant while both LAP and flow were simultaneously altered. Alveolar dead space ratio was not significantly different between the experimental groups. These changes in the alveolar dead space ratio indicate that FLOW 293t4.4 715246 for a given total ventilation, the fraction of ALV. zfp 44.8k3.9 29.9 -+3.1 ventilated, nonperfused alveoli is a function of the level of the PAP, which will in turn 89 11.952.5 22.0238 determine the relative amount of lung perfused. In this respect, our results agree Fig. 2. The effect of elevating flow at left atrial pressure of zero. See Fig. 1. EEP = 4.3 f 0.2 cm H,O; n with those of West and co-workers [26, 291 = 10. in a similar preparation, and with observa-

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tions made on intact animals, and patients with normal and altered pulmonary circulations [ 1,4,9, 13,241. On the other hand, we did not see a corz relation between PAP and venous admixture. In Group I, a constant flow was maintained, but the PAP was elevated by increasing LAP, resulting in a decrease in venous admixture. In Group II, the venous admixture increased when PAP was elevated by increasing the flow. In the third series of experiments, care was taken to maintain PAP constant while varying both LAP and flow. The venous admixture was markedly different (Fig. 3), and independent of the PAP. These variations in venous admixture depended upon how the PAP was changed, rather than upon the absolute value of the PAP. These results are in disagreement with those obtained by West [26], who found no change in venous admixture at different levels of flow and PAP. Our results are substantiated, at least partially, by findings that cardiac output and venous admixture change in parallel directions in a variety of experimental and clinical conditions [l, 4, 7, 131. We think that our data can be explained if one considers that the venous admixture was due, at least to a major extent, to unequal ventilation-to-perfusion relationships. When LAP was increased at constant flow, the same amount of flow perfused a larger portion of the lung. In that case, it is possible to conceive that flow was diverted away from relatively hyperperfused zones, to areas that were previously poorly perfused. This can explain not only the decrease in the alveolar dead space ratio, but also the decrease in venous admixture. On the other hand, when flow was elevated, again a larger area of the lung became perfused, as indicated by the decreasein the alveolar dead spaceratio, but the vertical gradient of distribution of flow was not affected. If this is the situation, relatively overperfused areas become more overly perfused, and this leads to an increase in the venous admixture. These experiments confirm that hemody-

namic alterations do result in variations in gas exchange. This may have special clinical relevance in patients with constant ventilation, as during surgery or with assisted ventilation. CONCLUSION The effects of elevating PAP on pulmonary gas exchange were evaluated in the isolated, upright, blood-dextran perfused dog lung. The PAP was elevated by two separate mechanisms, in the one case by elevating LAP, and the other by increasing total flow. We found that the alveolar dead space ratio was dependent upon the level of the PAP, and independent of the mechanism by which the PAP was elevated. However, the change in venous admixture was dependent upon the mechanism by which the PAP was elevated. By increasing the LAP, and thus the PAP, the venous admixture was decreased. On the other hand, by elevating the total flow, and thus the PAP, the venous admixture increased. In contrast with previous reports, we think that these changes are due to a redistribution of flow within the lung, and may have relevance clinically in patients on artificial ventilation. REFERENCES 1. Anthonisen, N. R., and Milic-Emili, J. Distribution of pulmonary perfusion in erect man. J. Appt. Physiol. 21:760, 1966. 2. Borst, H. G., McGregor, M., Whittenberger, J. L., and Berglund, S. Influences of pulmonary arterial and left atria1 pressures on pulmonary vascular resistance. Circ. Res. 4393, 1956. 3. Collins, J. A. The causes of progressive pulmonary insufficiency in surgical patients. J. Surg. Res. 9:685, 1969. 4. Dollery, C. T., and Hugh-Jones, P. Distribution of gas and blood in the lungs in disease. fir. Med. Bull. 19:59,1963. 5. Ellison, L. T. Physiological alterations in increased pulmonary blood flow with and without pulmonary hypertension. J. Appl. Physiol. 16:305, 1961. 6. Fowler, K. T., West, J. B., and Pain, M. C. F. Pressure-flow characteristics of horizontal lung preparations of minimal height. Resp. Physiol. 1:88, 1966. 7. Gonzalez, N. C., Overman, J., and Miner, M. E. Cardiopulmonary responsesto selective increase in

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