Mechanisms 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-PGF_1α production from −5.1 ± 4.4 to +12.6 ± 7.6 ng/kg·min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous P_O2 and decreased P_O2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing P_O2 or decreasing P_CO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had P_O2 and P_CO2 similar to fetal blood, blood with elevated O₂, and blood that had P_O2 and P_CO2 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 with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation.     

Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation

Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2-7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure.     

Effect of ventilation on pulmonary blood volume of the fetal lamb.

Blood volume changes in the fetal lung following the onset of ventilation were studied by isotopic measurement of red blood cell and plasma volume in rapidly frozen lungs of ten near term fetal lambs. Total pulmonary blood volumes of fetal lambs ventilated with 3% O2 and 7% CO2 in nitrogen (so that blood gas levels were little changed from fetal values), or with air, were compared with measurements in unventilated lambs. Regional correlations of blood volume and blood flow (measured with isotope-labeled microemboli) within the lungs were also examined. Total pulmonary blood volume averaged 5.6 ml/kg body weight in unventilated fetal lambs and was approximately 43% greated in fetal lambs after 5-20 min of air ventilation, but not significantly different in lambs ventilated with 3% O2 and 7% CO2 in nitrogen. Thus it is ventilation with air, rather than the introduction of gas into the alveoli, which enlarges the fetal pulmonary vascular bed. Regional pulmonary blood volume and blood flow were correlated, though poorly, in air-ventilated lungs, but not in lungs ventilated with 3% O2 and 7% CO2 in nitrogen; this suggests that a common factor may operate to increase both blood flow and blood volume in the fetal lung following the introduction of air.     

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.     

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.     

Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.     

EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs.

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.     

Placental gas exchange in the guinea-pig: fetal blood gas tensions following the reduction of maternal oxygen capacity with carbon monoxide

The effect of CO hypoxia on the placental exchange of respiratory gases was studied in anaesthetized pregnant guinea-pigs near term. Fetal PO2 and PCO2 were measured by mass spectrometry from a blood gas catheter in the right atrium. Administration of 5 ml CO over 65 s reduced maternal oxygen capacity by 26%. There was a rapid fall in fetal arterial PO2 and a more gradual rise in fetal PCO2. It was shown in separate experiments that the carboxyhaemoglobin content of fetal blood did not alter greatly in the first few min. after CO administration, which is the interval within which fetal PO2 was seen to fall. The alteration in fetal gas tensions can therefore be ascribed to the increased oxygen affinity and reduced oxygen capacity occasioned by the presence of carboxyhaemoglobin in the maternal blood. The alteration in placental oxygen transfer was calculated from the experimental findings, using a mathematical model of placental gas exchange in the guinea-pig. The total reduction in the oxygen transfer was 32% of the initial value. It was calculated that the reduction in maternal oxygen capacity was responsible for about two-thirds of this decrease, the remainder being due to the increased oxygen affinity of maternal blood.     

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.     

Ventilatory responses to partial cardiopulmonary bypass at rest and exercise in dogs

We determined the role of blood flow-induced changes in CO2 load to the lungs on ventilatory control, at rest and in the steady-state of electrically induced exercise, in the anesthetized dog. A portion of the vena caval blood was diverted to the descending aorta following "arterialization" through an extracorporeal gas exchanger. Ventilation typically decreased, both at rest and during exercise (i.e., at 2 different levels of mixed venous CO2), in proportion to the CO2 loss; arterial PCO2 was consequently regulated. There were concomitant increases of the pulmonary and peripheral vascular resistance. Bilateral cervical vagosympathectomy markedly attenuated the ventilatory response at rest, thus disrupting arterial PCO2 homeostasis, but not so during exercise. The results therefore provide evidence for and support the suggestion of CO2 flow-related hyperpnea both at rest and during muscular exercise.     

Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs.

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6-7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.     

Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation

Prolonged infusions of 17beta-estradiol reduce fetal pulmonary vascular resistance (PVR), but the effects of endogenous estrogens in the fetal pulmonary circulation are unknown. To test the hypothesis that endogenous estrogen promotes pulmonary vasodilation at birth, we studied the hemodynamic effects of prolonged estrogen-receptor blockade during late gestation and at birth in fetal lambs. We treated chronically prepared fetal lambs with ICI-182,780 (ICI, a specific estrogen-receptor blocker, n = 5) or 1% DMSO (CTRL, n = 5) for 7 days and then measured pulmonary hemodynamic responses to ventilation with low- and high-fraction inspired oxygen (FI(O(2))). Treatment with ICI did not change basal fetal PVR or arterial blood gas tensions. However, treatment with ICI abolished the vasodilator response to ventilation with low FI(O(2)) [change in PVR -30 +/- 6% (CTRL) vs. +10 +/- 13%, (ICI), P < 0.05] without reducing the vasodilator response to ventilation with high FI(O(2)) [change in PVR, -73 +/- 3% (CTRL) vs. -77 +/- 4%, (ICI); P = not significant]. ICI treatment reduced prostacyclin synthase (PGIS) expression by 33% (P < 0.05) without altering expression of endothelial nitric oxide synthase or cyclooxygenase-1 and -2. In situ hybridization and immunohistochemistry revealed that PGIS is predominantly expressed in the airway epithelium of late gestation fetal lambs. We conclude that prolonged estrogen-receptor blockade inhibits the pulmonary vasodilator response at birth and that this effect may be mediated by downregulation of PGIS. We speculate that estrogen exposure during late gestation prepares the pulmonary circulation for postnatal adaptation.     

Prostacyclin does not change during an oxygen induced increase in pulmonary blood flow in the fetal lamb

The role of prostacyclin in mediating the increase in pulmonary blood flow caused by an increase in oxygen tension in the fetal lamb was investigated. Plasma concentrations of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin, were measured during an increase in pulmonary blood flow caused by a rise in oxygen tension in eight intrauterine fetal lambs. Fetal oxygen tension was increased by placing the pregnant ewes in a hyperbaric chamber and having them breathe 100% oxygen at three atmospheres absolute pressure. This increased fetal PaO2 from 27 +/- 3 to 60 +/- 6 torr (mean +/- S.E., p less than or equal to 0.0001) and increased the proportion of right ventricular output distributed to the fetal lungs from 6 +/- 2 to 45 +/- 7% (mean +/- S.E., p less than or equal to 0.001). However, the fetal plasma concentration of 6-keto-PGF1 alpha did not change, 186 +/- 26 to 208 +/- 40 pg/ml (mean +/- S.E.). Indomethacin decreased plasma concentrations of 6-keto-PGF1 alpha in each of three fetuses but did not decrease the proportion of right ventricular output distributed to their lungs. The increase in pulmonary blood flow caused by an increase in oxygen tension in the fetal lamb is not associated with an increase in plasma concentrations of 6-keto-PGF1 alpha. Prostacyclin does not appear to be involved in the increase in pulmonary blood flow caused by the increase in oxygen tension at birth.     

Respiratory effects of the Jarvik-7 artificial heart

In five anesthetized patients with a Jarvik-7 artificial heart, pulmonary volume displacements generated by cardiogenic oscillations were measured using an indirect spirometric method. Consequences on gas exchange were also evaluated during a 15-min period of apnea by use of a tracheal insufflation of pure O2 at a constant flow rate of 20 l/min. The Jarvik-7 artificial heart generated a mean pulmonary volume displacement of 105 +/- 29 (SD) ml/heart beat. After 15 min of apnea, arterial PCO2 (PaCO2) significantly increased from 29 +/- 5 to 47 +/- 6 (SD) Torr. PaCO2 increased by 0.8 Torr/min from the 5th to the 15th min of apnea. Mean arterial PO2, mean pulmonary shunt, mean O2 consumption, and mean metabolic production of CO2 did not change significantly during the apnea period. Because cardiac output was kept constant during the study, O2 transport was adequately maintained throughout the apnea period. In patient 1, where the period of apnea was continued for 60 min, PaCO2 progressively increased until the 45th min and then remained stable at 61 Torr during the last 15 min of apnea. This "plateau" corresponded to an alveolar ventilation of 3,907 ml/min, representing 69% of the alveolar ventilation calculated during conventional mechanical ventilation. In conclusion, the Jarvik-7 artificial heart provides a potent respiratory support through the cardiogenic oscillations it generates.     

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.     

Changes in respiratory control in humans induced by 8 h of hyperoxia.

In humans, 8 h of isocapnic hypoxia causes a progressive rise in ventilation associated with increases in the acute ventilatory responses to hypoxia (AHVR) and hypercapnia (AHCVR). To determine whether 8 h of hyperoxia causes the converse of these effects, three 8-h protocols were compared in 14 subjects: 1) poikilocapnic hyperoxia, with end-tidal PO(2) (PET(O(2))) = 300 Torr and end-tidal PCO(2) (PET(CO(2))) uncontrolled; 2) isocapnic hyperoxia, with PET(O(2)) = 300 Torr and PET(CO(2)) maintained at the subject's normal air-breathing level; and 3) control. Ventilation was measured hourly. AHVR and AHCVR were determined before and 0.5 h after each exposure. During isocapnic hyperoxia, after an initial increase, ventilation progressively declined (P < 0.01, ANOVA). After exposure to hyperoxia, 1) AHVR declined (P < 0.05); 2) ventilation at fixed PET(CO(2)) decreased (P < 0.05); and 3) air-breathing PET(CO(2)) increased (P < 0.05); but 4) no significant changes in AHCVR or intercept were demonstrated. In conclusion, 8 h of hyperoxia have some effects opposite to those found with 8 h of hypoxia, indicating that there may be some "acclimatization to hypoxia" at normal sea-level values of PO(2).     

Gas exchange in healthy rabbits during high-frequency oscillatory ventilation

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.     

Human respiration at rest in rapid compression and at high pressures and gas densities

Ventilation (V), end-tidal PCO2 (PACO2), and CO2 elimination rate were measured in men at rest breathing CO2-free gas over the pressure range 1-50 ATA and the gas density range 0.4-25 g/l, during slow and rapid compressions, at stable elevated ambient pressures and during slow decompressions in several phases of Predictive Studies III-1971 and Predictive Studies IV-1975. Inspired O2 was at or near natural O2 levels during compressions and at stable high pressures; it was 0.5 ATA during decompressions. Rapid compressions to high pressures did not impair respiratory homeostasis. Progressive increase in pulmonary gas flow resistance due to elevation of ambient pressure and inspired gas density to the He-O2 equivalent of 5,000 feet of seawater was not observed to progressively decrease resting V, or to progressively increase resting PACO2. Rather, a complex pattern of change in PACO2 was seen. As both ambient pressure and pulmonary gas flow resistance were progressively raised, PACO2 at first increased, went through a maximum, and then declined towards values near the 1 ATA level. It is suggested that this pattern of PACO2 change results from interaction on ventilation of 1) increase in pulmonary resistance due to elevation of gas density with 2) increase in respiratory drive postulated as due to generalized CNS excitation associated with exposure to high hydrostatic pressure. There may be a similar interaction between increased gas flow resistance and increase in respiratory drive related to nitrogen partial pressure and the narcosis resulting therefrom.     

Respiratory stimulation by female hormones in awake male rats.

The respiratory effect of progestin differs among various animal species and humans. The rat does not hyperventilate in response to exogenous progestin. The present study was conducted to determine whether administration of combined progestin and estrogen prompts ventilatory stimulation in the male rat. Ventilation, blood gases, and metabolic rates (O2 consumption and CO2 production) were measured in the awake and unrestrained male Wistar rat. The combined administration of a synthetic potent progestin (TZP4238) and estradiol for 5 days significantly increased tidal volume and minute expiratory ventilation (VE), reduced arterial PCO2, and enhanced the ventilatory response to CO2 inhalation (delta VE/delta PCO2). On the other hand, respiratory frequency, O2 consumption, CO2 production, and body temperature were not affected. The arterial pH increased slightly, with a concomitant decrease in plasma [HCO3-]. Administration of either TZP4238 or estradiol alone or vehicle (Tween 80) had no effect on respiration, blood gases, and ventilatory response to CO2. The results indicated that respiratory stimulation following combined progestin plus estradiol treatment in the male rat involves activation of process(es) that regulate tidal volume and its augmentation during CO2 stimulus.     

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.