Blood-gas equilibration of CO2 and O2 in lungs of awake dogs during prolonged rebreathing

To reinvestigate the blood-gas CO2 equilibrium in lungs, rebreathing experiments were performed in five unanesthetized dogs prepared with a chronic tracheostomy and an exteriorized carotid loop. The rebreathing bag was initially filled with a gas mixture containing 6-8% CO2, 12, 21, or 39% O2, and 1% He in N2. During 4-6 min of rebreathing PO2 in the bag was kept constant by a controlled supply of O2 while PCO2 rose steadily from approximately 40 to 75 Torr. Spot samples of arterial blood were taken from the carotid loop; their PCO2 and PO2 were measured by electrodes and compared with the simultaneous values of end-tidal gas read from a mass spectrometer record. The mean end-tidal-to-arterial PO2 differences averaging 16, 4, and 0 Torr with bag PO2 about 260, 130, and 75 Torr, respectively, were in accordance with a venous admixture of about 1%. No substantial PCO2 differences between arterial blood and end-tidal gas (PaCO2 - PE'CO2) were found. The mean PaCO2 - PE'CO2 of 266 measurements in 70 rebreathing periods was -0.4 +/- 1.4 (SD) Torr. There was no correlation between PaCO2 - PE'CO2 and the level of arterial PCO2 or PO2. The mean PaCO2 - PE'CO2 became +0.1 Torr when the blood transit time from lungs to carotid artery (estimated at 6 s) and the rate of rise of bag PCO2 (4.5 Torr/min) were taken into account. These experimental results do not confirm the presence of significant PCO2 differences between arterial blood and alveolar gas in rebreathing equilibrium.     

End-tidal CO2 response to low levels of inspired CO2 in awake beagle dogs

The steady-state end-tidal CO2 tension (PCO2) was examined during control and 1% CO2 inhalation periods in awake beagle dogs with an intact airway breathing through a low dead-space respiratory mask. A total of eight experiments were performed in four dogs, comprising 31 control observations and 23 CO2 inhalation observations. The 1% inhaled CO2 produced a significant increase in the steady-state end-tidal PCO2 comparable to the expected 1 Torr predicted from conventional CO2 control of ventilation. We conclude that 1% inhaled CO2 results in a hypercapnia. Any protocol that is to resolve the question of whether mechanisms are acting during low levels of inhaled CO2 such that ventilation increases without any change in arterial PCO2 must have sufficient resolving power to discriminate changes in gas tension in magnitude predicted from conventional (i.e., arterial PCO2) control of ventilation.     

Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.     

Control of ventilation during exercise in patients with central venous-to-systemic arterial shunts

The diversion of systemic venous blood into the arterial circulation in patients with intracardiac right-to-left shunts represents a pathophysiological condition in which there are alterations in some of the potential stimuli for the exercise hyperpnea. We therefore studied 18 adult patients with congenital (16) or noncongenital (2) right-to-left shunts and a group of normal control subjects during constant work rate and progressive work rate exercise to assess the effects of these alterations on the dynamics of exercise ventilation and gas exchange. Minute ventilation (VE) was significantly higher in the patients than in the controls, both at rest (10.7 +/- 2.4 vs. 7.5 +/- 1.2 l/min, respectively) and during constant-load exercise (24.9 +/- 4.8 vs. 12.7 +/- 2.61 l/min, respectively). When beginning constant work rate exercise from rest, the ventilatory response of the patients followed a pattern that was distinct from that of the normal subjects. At the onset of exercise, the patients' end-tidal PCO2 decreased, end-tidal PO2 increased, and gas exchange ratio increased, indicating that pulmonary blood was hyperventilated relative to the resting state. However, arterial blood gases, in six patients in which they were measured, revealed that despite the large VE response to exercise, arterial pH and PCO2 were not significantly different from resting values when sampled during the first 2 min of moderate-intensity exercise. Arterial PCO2 changed by an average of only 1.4 Torr after 4.5-6 min of exercise. Thus the exercise-induced alveolar and pulmonary capillary hypocapnia was of an appropriate degree to compensate for the shunting of CO2-rich venous blood into the systemic arterial circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary function of the green sea turtle, Chelonia mydas

Lung volumes, oxygen uptake (VO2), end-tidal PO2, and PCO2, diffusing capacity of the lungs for CO (DLCO), pulmonary blood flow (QL) and respiratory frequency were measured in the green sea turtle (Chelonia mydas) (49-127 kg body wt). Mean lung volume (VL) determined from helium dilution was 57 ml/kg and physiological dead space volume (VD) was about 3.6 ml/kg. QL, determined from acetylene uptake during rebreathing, increased in proportion to VO2 with temperature. Therefore, constant O2 content difference was maintained between pulmonary arterial and venous blood. DLCO, measured using a rebreathing technique, was 0.04 ml X kg-1 X min-1 X Torr-1 at 25 degrees C. Several cardiopulmonary characteristics in C. mydas are advantageous to diving: large tidal volume relative to functional residual capacity promotes fast exchange of the alveolar gas when the turtle surfaces for breathing: and the concomitant rise of pulmonary blood flow and O2 uptake with temperature assures efficient O2 transport regardless of wide temperature variations encountered during migrations.     

Alveolar PCO2 oscillations and ventilation at sea level and at high altitude.

This study examines the potential for a ventilatory drive, independent of mean PCO2, but depending instead on changes in PCO2 that occur during the respiratory cycle. This responsiveness is referred to here as "dynamic ventilatory sensitivity." The normal, spontaneous, respiratory oscillations in alveolar PCO2 have been modified with inspiratory pulses approximating alveolar PCO2 concentrations, both at sea level and at high altitude (5,000 m, 16,400 ft.). All tests were conducted with subjects exercising on a cycle ergometer at 60 W. The pulses last about half the inspiratory duration and are timed to arrive in the alveoli during early or late inspiration. Differences in ventilation, which then occur in the face of similar end-tidal PCO2 values, are taken to result from dynamic ventilatory sensitivity. Highly significant ventilatory responses (early pulse response greater than late) occurred in hypoxia and normoxia at sea level and after more than 4 days at 5,000 m. The response at high altitude was eliminated by normalizing PO2 and was reduced or eliminated with acetazolamide. No response was present soon after arrival (<4 days) at base camp, 5,000 m, on either of two high-altitude expeditions (BMEME, 1994, and Kanchenjunga, 1998). The largest responses at 5,000 m were obtained in subjects returning from very high altitude (7,100-8,848 m). The present study confirms and extends previous investigations that suggest that alveolar PCO2 oscillations provide a feedback signal for respiratory control, independent of changes in mean PCO2, suggesting that natural PCO2 oscillations drive breathing in exercise.     

Umbilical cord occlusion stimulates breathing independent of blood gases and pH

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated by use of 16 unanesthetized fetal sheep near full term. Artificial ventilation with high-frequency oscillation was used to control fetal arterial blood gas tensions. At baseline, PCO2 was maintained at control fetal values and PO2 was elevated to between 25 and 50 Torr. In the first study on six intact and four vagotomized fetuses, arterial PCO2 and PO2 were maintained constant during two 30-min periods of umbilical cord occlusion. Nevertheless, the mean fetal breathing rate increased significantly when the umbilical cord was occluded. In the second study on six intact fetuses, hypercapnia (68 Torr) was imposed by adding CO2 to the ventilation gas. When the umbilical cord was occluded, there was a significantly greater stimulation of breathing (rate, incidence, and amplitude) in response to hypercapnia than in response to hypercapnia alone. During cord occlusion, plasma prostaglandin E2 concentration decreased significantly. Results indicate that cord occlusion stimulates breathing possibly by causing the removal of a placentally produced respiratory inhibitor such as prostaglandin E2 from the circulation.     

Evidence for a central action of CO2 ventilatory stimulus in Pekin ducks (author's transl)]

Ventilatory responses to changes in PCO2 of the blood perfusing the central nervous system were studied breath by breath by pneumotachography in Pekin ducks under transient and steady condition. 1. Transients. In conscious birds, all the arteries to the cephalic region were tied or clamped, except the right internal carotid. The blood supply via the single remaining arterial pathway was transiently replaced, for about 15 sec, by injecting 2 ml of blood previously made either normocapnic (control PCO2 = 32 Torr) or hypercapnic (test; PCO2 = 76 Torr) from a syringe thermostated at 41 degrees C, under normal oxygenation (PO2 around 110 Torr) and mean endovascular pressure (107 mm Hg). During control injections, no significant ventilatory changes were observed. In contrast, test injections provoked an early and significant 20% increase in the minute volume of ventilation. 2. Steady conditions. Using cross-perfusion between pairs of anesthetized ducks, the head of a recipient animal (R) was vascularly isolated from the trunk and perfused by a donor (D), the nervous connections with the trunk remaining intact. When giving some CO2 to breathe to D (FICO2 = 0.05) while R breathed ambient air, arterial PCO2 increased in D and in the head of R, and hyperventilation occurred in both ducks. As a consequence of this hyperventilation, PCO2 decreased in the arterial blood and the end-tidal gas of R.     

Respiratory effects in humans of a 5-day elevation of end-tidal PCO2 by 8 Torr.

The aims of this study were to determine 1) whether ventilatory adaptation occurred over a 5-day exposure to a constant elevation in end-tidal PCO2 and 2) whether such an exposure altered the sensitivity of the chemoreflexes to acute hypoxia and hypercapnia. Ten healthy human subjects were studied over a period of 13 days. Their ventilation, chemoreflex sensitivities, and acid-base status were measured daily before, during, and after 5 days of elevated end-tidal PCO2 at 8 Torr above normal. There was no major adaptation of ventilation during the 5 days of hypercapnic exposure. There was an increase in ventilatory chemosensitivity to acute hypoxia (from 1.35 +/- 0.08 to 1.70 +/- 0.07 l/min/%; P < 0.01) but no change in ventilatory chemosensitivity to acute hypercapnia. There was a degree of compensatory metabolic alkalosis. The results do not support the hypothesis that the ventilatory adaptation to chronic hypercapnia would be much greater with constant elevation of alveolar PCO2 than with constant elevation of inspired PCO2, as has been used in previous studies and in which the feedback loop between ventilation and alveolar PCO2 is left intact.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Cardiac receptors evoke ventilatory response with increased venous PCO2 at constant arterial PCO2

The effects of elevated venous PCO2 and denervation of the cardiac ventricles on ventilation were studied in 20 anesthetized open-chest unidirectionally ventilated White Leghorn cockerels. Venous PCO2 was increased by insufflating the gut with high CO2 while recording changes in the amplitude of the sternal movements. Arterial blood gases were held constant by unidirectionally ventilating the lungs with gas flows approximately five times the animal's resting minute volume. Insufflating the gut with 90% N2-10% O2 did not change the level of ventilation, whereas with 90% CO2-10% O2 the amplitude of sternal movement increased 500% above that with no gut gas flow. Exchange of N2 for the CO2 was followed by a rapid reduction of ventilatory movements to control levels. Arterial blood gases remained constant during gut gas insufflation, whereas mixed venous PCO2 increased and mixed venous pH decreased when high CO2 was given to the gut. Cutting the middle cardiac nerves, which primarily innervate the ventricles of the heart, reduced the ventilatory response to CO2 gut insufflation by 67%. Sympathetic denervation of the thoracic viscera did not change the responses. It appears that, in the chicken, increasing the mixed venous PCO2 while holding the arterial blood gases constant alters ventilation by an afferent system located in the venous circulation or in the right ventricle which is sensitive to changes in PCO2.     

CO2 and mechanical factors reduce blood flow in a collapsed lung lobe

Left lower lobe-to-total blood flow ratio (Ql/QT) was measured with electromagnetic flow probes in anesthetized open-chest dogs. There was a 66% reduction in Ql/QT during lobar collapse, a 53% reduction during lobar ventilation hypoxia with pulmonary venous PO2 and PCO2 equal to mixed venous tensions, and a 45% reduction during a similar degree of ventilation hypoxia but with normal end-tidal PCO2. We concluded that the reduction in blood flow during lobar collapse is due predominantly to hypoxic vasoconstriction, but that this mechanism is augmented by the raised PCO2 and mechanical factors present during collapse.     

A visual aid for teaching ventilation-perfusion relationships

To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology.     

Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study.

The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia.

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial PO2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal PO2 was held at 55 Torr and end-tidal PCO2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH (P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial PO2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.     

Periodic breathing in the crocodile, Crocodylus niloticus: consequences for the gas exchange ratio and control of breathing.

The ventilatory pattern in the Nile crocodile consists of episodes of breathing, interrupted by periods of breath-holding, the latter occupying 80% of total time during normal breathing at 25 degrees C. End-tidal gas composition varied with the periodic breathing but PO2 was always high (PO2 less than 110 torr) and PCO2 low (PCO2 less than 25 torr). The alveolar gas exchange ratio, RE, was very low during the non-ventilatory periods (RE congruent to 0.5), but increased markedly during ventilation. Breathing of hypoxic and hpercapnic gases caused a pronounced decrease in the duration of breath-holds. Hypercapnia decreased breathing frequency during ventilatory periods, but increased tidal volume. The results are discussed in relation to the practice of prolonged breath-holding associated with diving in crocodiles.     

Gas density dependence of regional VA/V and VA/Q inequality during constant-flow ventilation

Constant-flow ventilation (CFV) is achieved by delivering a constant stream of inspiratory gas through cannulas aimed down the main stem bronchi at flow rates totaling 1-3 l.kg-1.min-1 in the absence of tidal lung motion. Previous studies have shown that CFV can maintain a normal arterial PCO2, although significant ventilation-perfusion (VA/Q) inequality appears. This VA/Q mismatch could be due to regional differences in lung inflation that occur during CFV secondary to momentum transfer from the inflowing stream to resident gas in the lung. We tested the hypothesis that substitution of a gas with lower density might attenuate regional differences in alveolar pressure and reduce the VA/Q inequality during CFV. Gas exchange was studied in seven anesthetized dogs by the multiple inert gas elimination technique during ventilation with intermittent positive-pressure ventilation, CFV with O2-enriched nitrogen (CFV-N2), or CFV with O2-enriched helium (CFV-He). As an index of VA/Q inequality independent of shunt, the log SD blood flow increased from 0.757 +/- 0.272 during intermittent positive-pressure ventilation to 1.54 +/- 0.36 (P less than 0.001) during CFV-N2. Switching from CFV-N2 to CFV-He at the same flow rate did not improve log SD blood flow (1.45 +/- 0.21) (P greater than 0.05) but tended to increase arterial PCO2. In excised lungs with alveolar capsules attached to the pleural surface, CFV-He significantly reduced alveolar pressure differences among lobes compared with CFV-N2 as predicted. Regional alveolar washout of Ar after a stap change of inspired concentration was slower during CFV--He than during CFV-N2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local regulation of pulmonary blood flow and ventilation-perfusion ratios in the coatimundi.

Small catheters (ca. 3 mm diam at tip) were wedged in subsegmental bronchi in anesthetized coatimundi (Nasua nasua) during spontaneous breathing. Mixed expired gases of a group of lobules were sampled continuously without contamination from neighboring units, and local tidal volume, frequency, carbon dioxide production, and oxygen consumption were measured, as well as mixed venous PO2 and PCO2. Local ventilation-perfusion ratio, alveolar PO2, PCO2, and blood flow were calculated. There was a 22% reduction (range 15-38) in local perfusion (as percent of flow at PAO2 100 mmHg) per 10 mmHg fall in local alveolar oxygen tension over the PAO2 range 150-36 mmHg. Local hypercapnia had little effect on local flow. Local tidal volume (ca. 1% of total tidal volume) was unaffected by changes in alveolar gas tensions. The contribution of vasoconstriction or vasodilatation, as a negative feedback system, to the stability of local PAO2 was greatest close to the physiologic range (65-85 mmHg) falloderate efficiency.     

Splanchnic hemodynamics and gut mucosal-arterial PCO(2) gradient during systemic hypocapnia.

The effects of hypocapnia [arterial PCO(2) (Pa(CO(2))) 15 Torr] on splanchnic hemodynamics and gut mucosal-arterial P(CO(2)) were studied in seven anesthetized ventilated dogs. Ileal mucosal and serosal blood flow were estimated by using laser Doppler flowmetry, mucosal PCO(2) was measured continuously by using capnometric recirculating gas tonometry, and serosal surface PO(2) was assessed by using a polarographic electrode. Hypocapnia was induced by removal of dead space and was maintained for 45 min, followed by 45 min of eucapnia. Mean Pa(CO(2)) at baseline was 38.1 +/- 1.1 (SE) Torr and decreased to 13.8 +/- 1.3 Torr after removal of dead space. Cardiac output and portal blood flow decreased significantly with hypocapnia. Similarly, mucosal and serosal blood flow decreased by 15 +/- 4 and by 34 +/- 7%, respectively. Also, an increase in the mucosal-arterial PCO(2) gradient of 10.7 Torr and a reduction in serosal PO(2) of 30 Torr were observed with hypocapnia (P < 0.01 for both). Hypocapnia caused ileal mucosal and serosal hypoperfusion, with redistribution of flow favoring the mucosa, accompanied by increased PCO(2) gradient and diminished serosal PO(2).     

Mechanism of stimulation of pulmonary prostacyclin synthesis at birth

In order to investigate the mechanism behind ventilation-induced pulmonary prostacyclin production at birth, chloralose anesthetized, exteriorized, fetal lambs were ventilated with a gas mixture that did not change blood gases (fetal gas) and unventilated fetal lungs were perfused with blood containing increased O2 and decreased CO2. Ventilation with fetal gas (3%O2, 5%CO2) increased net pulmonary prostacyclin (as 6-keto-PGF1 alpha) production from -5.1 +/- 4.4 to +12.6 +/- 7.6 ng/kg X min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous PO2 and decreased PCO2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing PO2 or decreasing PCO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had PO2 and PCO2 similar to fetal blood, blood with elevated O2, and blood that had PO2 and PCO2 values similar to arterial blood of newborn animals. Neither increased O2 nor decreased CO2 in the blood perfusing the lungs stimulated pulmonary prostacyclin synthesis. We conclude that the mechanism responsible for the stimulation of pulmonary prostacyclin production with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation.