Ventilatory and metabolic responses of burrowing owls, Athene cunicularia, to moderate and extreme hypoxia: analysis of the hypoxic ventilatory threshold vs. hemoglobin oxygen affinity relationship in birds

We measured ventilation, oxygen consumption and blood gases in burrowing owls (Athene cunicularia) breathing moderate and extreme hypoxic gas mixtures to determine their hypoxic ventilatory threshold (HVT) and to assess if they, like other birds and mammals, exhibit a relationship between HVT and hemoglobin O2 affinity (P(50)) of their blood. An earlier report of an attenuated ventilatory responsiveness of this species to hypoxia was enigmatic given the low O2 affinity (high P(50)) of burrowing owl hemoglobin. In the current study, burrowing owls breathing 11% and 9% O2 showed a significantly elevated total ventilation. The arterial partial pressure of oxygen (PaO2) at which ventilation is elevated above normoxic values in burrowing owls was 58 mm Hg. This threshold value conforms well to expectations based on the high P(50) of their hemoglobin and the HVT vs. P(50) relationship for birds developed in this study. Correcting for phylogenetic relatedness in the multi-species analysis had no effect on the HVT vs. P(50) relationship. Also, because burrowing owls in this study did not show a hypometabolic response at any level of hypoxia (even at 9% O2); HVT described in terms of percent change in oxygen convection requirement is identical to that based on ventilation alone.     

Ventilatory and metabolic responses of burrowing owls, Athene cunicularia, to moderate and extreme hypoxia: analysis of the hypoxic ventilatory threshold vs. hemoglobin oxygen affinity relationship in birds.

We measured ventilation, oxygen consumption and blood gases in burrowing owls (Athene cunicularia) breathing moderate and extreme hypoxic gas mixtures to determine their hypoxic ventilatory threshold (HVT) and to assess if they, like other birds and mammals, exhibit a relationship between HVT and hemoglobin O2 affinity (P(50)) of their blood. An earlier report of an attenuated ventilatory responsiveness of this species to hypoxia was enigmatic given the low O2 affinity (high P(50)) of burrowing owl hemoglobin. In the current study, burrowing owls breathing 11% and 9% O2 showed a significantly elevated total ventilation. The arterial partial pressure of oxygen (PaO2) at which ventilation is elevated above normoxic values in burrowing owls was 58 mm Hg. This threshold value conforms well to expectations based on the high P(50) of their hemoglobin and the HVT vs. P(50) relationship for birds developed in this study. Correcting for phylogenetic relatedness in the multi-species analysis had no effect on the HVT vs. P(50) relationship. Also, because burrowing owls in this study did not show a hypometabolic response at any level of hypoxia (even at 9% O2); HVT described in terms of percent change in oxygen convection requirement is identical to that based on ventilation alone.     

Estimation of human fetal-placental unit metabolic rate by application of the Bohr principle

The Bohr Principle via continuous indirect calorimetry was used to estimate human fetal-placental unit metabolic rate in 12 normal women undergoing elective caesarean section under continuous lumbar epidural anaesthesia. Maternal oxygen consumption decreased after umbilical cord clamping and after placental removal. Fetal-placental unit oxygen consumption was 10.7 +/- 1.3 ml/min per kg (mean +/- SEM). Fetal oxygen consumption was 6.8 +/- 1.4 ml/min per kg. Placental oxygen consumption was 37 +/- 12 ml/min per kg. Fetal-placental unit carbon dioxide production was 9.2 +/- 1.2 ml/min per kg. These mean values agree favourably with measurements of uterine and fetal metabolism from other mammalian species. Maternal minute ventilation decreased with removal of the fetal-placental unit, and this decrease was found to be linearly related to the fetal-placental unit carbon dioxide production.     

Respiratory and cardiovascular effects of thyrotropin-releasing hormone as modified by isoflurane, enflurane, pentobarbital and ketamine

Thyrotropin-releasing hormone (TRH) possesses significant arousing and cardio-respiratory stimulant actions. The effects of a 2 mg/kg i.v. bolus dose of TRH on respiration and systemic hemodynamics were compared in conscious, freely-moving rats and during anesthesia with 4 different anesthetics. Fifty-four male Sprague-Dawley rats weighing 285 +/- 4 g (mean +/- S.E.M.) were divided into 5 groups: conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (8 mg/kg/h i.v.), and ketamine (60 mg/kg/h i.v.). Anesthetized rats were intubated and breathed oxygen or anesthetic/oxygen spontaneously. Aortic blood pressure, heart rate, cardiac output, respiratory rate, arterial blood pH, blood gases, lactate and glucose were measured, and data were collected over a 20 min baseline period and for 130 min post-TRH. TRH increased respiratory rate in all groups; concomitant changes in arterial PCO2 indicated increased minute ventilation in the inhalation agent groups but not in the i.v. anesthetic groups or in the awake group. Significant respiratory depression in the enflurane group was rapidly reversed by TRH. The respiratory stimulant and arousing effects of TRH were smallest with ketamine anesthesia. The hemodynamic responses to TRH were consistent with a pattern of sympathoadrenalmedullary activation and were relatively uniform across groups despite anesthetic-induced alterations in baseline values. TRH or its analogues may prove useful as an analeptic in clinical anesthesia.     

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Opioids depress respiration and decrease chest wall compliance. A previous study in this laboratory showed that dopamine-D(1) receptor (D(1)R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D(1)R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 +/- 3.4 microg/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO(2)), elevated end-tidal carbon dioxide (ETCO(2)), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 microg/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D(1)R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO(2) and ETCO(2) to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 +/- 4.3 microg/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D(1)R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia.     

Oxygen consumption is maintained in fetal sheep during prolonged hypoxaemia.

Experiments were conducted in 12 chronically-catheterized pregnant sheep to examine the effect of prolonged hypoxaemia secondary to the restriction of uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days gestation to place a teflon vascular occluder around the maternal common internal iliac artery and for insertion of vascular catheters. Following a 5-day recovery period, uterine blood flow was reduced in 6 animals for 24 hours and in 6 animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/- 2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours respectively in the experimental group and did not change the control group. Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and 24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations remained elevated throughout the experimental period with maximum concentrations of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l during the control period. Umbilical blood flow increased from 186 +/- 19 ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21 ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and 0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Meclofenamate increases ventilation in lambs

To investigate the effects of the prostaglandin synthetase inhibitor, meclofenamate, on postnatal ventilation, we studied 11 unanaesthetised, spontaneously-breathing lambs at an average age of 7.9 +/- 1.1 days (SEM; range 5-14 days) and an average weight of 4.9 +/- 0.5 kg (range 3.0-7.0 kg). After a 30-min control period we infused 4.23 mg/kg meclofenamate over 10 min and then gave 0.23 mg/h per kg for the remainder of the 4 h. Ventilation increased progressively from a control value of 515 +/- 72 ml/min per kg to a maximum of 753 +/- 100 ml/min per kg after 3h of infusion (P less than 0.05) due to an increased breathing rate; the effects were similar during both high- and low-voltage electrocortical activity. There were no significant changes in tidal volume, heart rate, blood pressure, arterial pH or PaCO2, the increased ventilation resulted from either an increase in dead space ventilation or an increase in CO2 production. This study indicates that meclofenamate causes an increase in ventilation in lambs but no changes in pH of PaCO2. The mechanism and site of action remain to be defined.     

Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children.

To assess effects of anesthesia and opioids, we studied 13 children with obstructive sleep apnea (OSA, age 4.0 +/- 2.2 yr, mean +/- SD) and 24 age-matched control subjects (5.8 +/- 4.0 yr). Apnea indexes of children with OSA were 29.4 +/- 18 h-1, median 30 h-1. Under inhalational anesthetic, closing pressure at the mask was 2.2 +/- 6.9 vs. -14.7 +/- 7.8 cmH2O, OSA vs. control (P < 0.001). After intubation, spontaneous ventilation was 115.5 +/- 56.9 vs. 158.7 +/- 81.6 ml x kg-1 small middle dot min-1, OSA vs. control (P = 0.02), despite elevated PCO2 (49.3 vs. 42.1 Torr, OSA vs. control, P < 0.001). Minute ventilation fell after fentanyl (0.5 microg/kg iv), with central apnea in 6 of 13 OSA cases vs. 1 of 23 control subjects (P < 0.001). Consistent with the finding of reduced spontaneous ventilation, apnea was most likely when end-tidal CO2 exceeded 50 Torr during spontaneous breathing under anesthetic. Thus children with OSA had depressed spontaneous ventilation under anesthesia, and opioids precipitated apnea in almost 50% of children with OSA who were intubated but breathing spontaneously under inhalational anesthesia.     

Changes in cardiac output during sustained maximal ventilation in humans

To determine the increment in cardiac output and in O2 consumption (Vo2) from quiet breathing to maximal sustained ventilation, Vo2 and cardiac output were measured using an acetylene rebreathing technique in five subjects. Cardiac output and Vo2 were measured multiple times in each subject at rest and during sustained maximal ventilation. During maximal ventilation subjects breathed 5% CO2 to prevent hypocapnia. The increase in cardiac output from rest to maximal breathing was taken as an estimate of respiratory muscle blood flow and was used to calculate the arteriovenous O2 content difference across the respiratory muscles from the Fick equation. Cardiac output increased by 4.3 +/- 1.0 l/min (mean +/- SD), from 5.6 +/- 0.7 l/min at rest to 9.9 +/- 1.1 l/min, during maximal ventilations ranging from 127 to 193 l/min. Vo2 increased from 312 +/- 29 to 723 +/- 69 ml/min during maximal ventilation. O2 extraction across the respiratory muscles during maximal breathing was 9.6 +/- 1.0 vol% (range 8.5 to 10.7 vol%). These values suggest an upper limit of respiratory muscle blood flow of 3-5 l/min during unloaded maximal sustained ventilation.     

Respiratory consequences of feeding in the snake Python molorus

Snakes can ingest large meals and exhibit marked increases in metabolic rate during digestion. Because postprandial oxygen consumption in some snakes may surpass that attained during exercise, studies of digestion offers an alternative avenue to understand the cardio-respiratory responses to elevated metabolic rate in reptiles. The effects of feeding on metabolic rate, arterial oxygen levels, and arterial acid-base status in the snake Python molorus are described. Four snakes (180-250 g) were cannulated in the dorsal aorta and blood samples were obtained during 72 h following ingestion of a meal (rat pups) exceeding 20% of body weight. Oxygen consumption increased from a fasting value of 1.71 +/- 0.08 to 5.54 +/- 0.42 ml kg-1 min-1 at 48 h following feeding, and the respiratory gas exchange ratio increased from 0.67 +/- 0.02 to a maximum of 0.92 +/- 0.03 at 32 h. Plasma lactate was always less than 0.5 mM, so the postprandial increase in metabolic rate was met by aerobic respiration. In fasting animals, arterial PO2 was 66 +/- 4 mmHg and haemoglobin-O2 saturation was 92 +/- 3%; similar values were recorded during digestion, but haematocrit decreased from 15.8 +/- 1.0 to 9.8 +/- 0.8 due to repeated blood sampling. Plasma [HCO3-] increased from a fasting level of 19.3 +/- 0.8 to 25.8 +/- 1.0 mmol l-1 at 24 h after feeding. However, because arterial PCO2 increased from 21.1 +/- 0.5 to 27.9 +/- 1.4 mmHg, there was no significant change in arterial pH from the fasting value of 7.52 +/- 0.01. Acid-base status returned to pre-feeding levels at 72 h following feeding. The increased arterial PCO2 is most likely explained by a reduction in ventilation relative to metabolism, but we predict that lung PO2 does not decrease below 115 mmHg. Although ingestion of large meals is associated with large metabolic changes in pythons, the attendant changes in blood gases are relatively small. In particular, the small changes in plasma [HCO3-] and stable pH show that pythons respond very differently to digestion than alligators where very large alkaline tides have been observed. It is unclear why pythons and alligators differ in the magnitude of their responses, but given these interspecific differences it seems worthwhile to describe arterial blood gases during digestion in other species of ectothermic vertebrates.     

K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation

The role of ATP-sensitive K(+) (K(ATP)(+)) channels, nitric oxide, and adenosine in coronary exercise hyperemia was investigated. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus and instrumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of K(ATP)(+) channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (N(omega)-nitro-L-arginine, 35 mg/kg iv), and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During control exercise, myocardial oxygen consumption increased ~2.9-fold, coronary blood flow increased ~2.6-fold, and coronary venous oxygen tension decreased from 19.9 +/- 0.4 to 13.7 +/- 0.6 mmHg. Triple blockade did not significantly change the myocardial oxygen consumption or coronary blood flow response during exercise but lowered the resting coronary venous oxygen tension to 10.0 +/- 0.4 mmHg and during exercise to 6.2 +/- 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the adenosine receptor blockade. These results indicate that combined inhibition of K(ATP)(+) channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that these factors are not required for local metabolic coronary vasodilation during exercise.     

Oxygen consumption, carbon dioxide production and progestagen secretion in the intact ovary of the day-16 pregnant rat

Arterial and venous blood gases were measured in the ovary of the Day-16-pregnant rat by a Van Slyke manometric technique. Concurrent observations of progestagen concentrations were also made to determine rates of hormone secretion. The oxygen consumption was 196.5 +/- 28.4 ml/min per kg ovarian tissue (mean +/- s.e.m., n = 8) which is amongst the highest recorded from any organ. Carbon dioxide production was 149.8 +/- 36.6 ml/min per kg ovarian tissue (n = 5) and the respiratory quotient was 0.756 +/- 0.023 (n = 5), indicating that lipids are the major energy substrate used by the ovary. The rates of progestagen secretion were 2.12 +/- 0.37 and 0.42 +/- 0.10 nmol/min per ovary for progesterone and 20 alpha-dihydroprogesterone, respectively, and were not related to oxygen consumption. Less than 1.5% of the oxygen consumed was used in the essential conversion of cholesterol to pregnenolone, the immediate precursor of progesterone.     

Effects of 2,4-dinitrophenol on the body temperature and cardiopulmonary functions in unanaesthetized rats, Rattus Rattus

Infusion of 6–12 mg/kg 2,4-dinitrophenol in the awake rat causes cardiovascular and respiratory responses similar to those induced by physical activity. Respiratory rate, tidal volume and minute ventilation rises promptly following DNP infusion indicating that the response to DNP is activated via a reflex loop in respiratory control. On the other hand, heart rate increased gradually as a function of body temperature. The dosages of 6–12 mg/kg DNP are suitable for the awake rat to simulate exercise-induced cardiopulmonary responses.     

Development of body oxygen stores in harbor seals: effects of age, mass, and body composition

Harbor seal pups are highly precocial and can swim and dive at birth. Such behavioral maturity suggests that they may be born with mature body oxygen stores or that stores develop quickly during the nursing period. To test this hypothesis, we compared the blood and muscle oxygen stores of harbor seal pups, yearlings, and adults. We found that pups had smaller oxygen stores than adults (neonates 57%, weaned pups 75%, and yearlings 90% those of adults), largely because neonatal myoglobin concentrations were low (1.6+/-0.2 g% vs. 3.8+/-0.3 g% for adults) and changed little during the nursing period. In contrast, blood oxygen stores were relatively mature, with nursing pups having hematocrit (55%+/-0.2%), hemoglobin (21.7+/-0.4 g%), and blood volume (12.3+/-0.5 mL/kg) only slightly lower than the corresponding values for adults (57%+/-0.2%, 23.8+/-0.3 g %, and 15.0+/-0.5 mL/kg). Because neonatal pups had relatively high metabolic rates (11.0 mL O2/kg min), their calculated aerobic dive limit was less than 50% that of adults. These results suggest that harbor seals' early aquatic activity is primarily supported by rapid development of blood, with immature muscle oxygen stores and elevated use rates limiting aerobic diving ability.     

Involvement of vagal opioid receptors in respiratory effects of morphine in anaesthetized rats.

Respiratory effects of morphine injection to the femoral vein were investigated in urethane and chloralose anaesthetized and spontaneously breathing rats, prior to and after midcervical vagotomy. Bolus injection of morphine HCl at a dose of 2 mg/kg of body weight induced depression of ventilation in all rats, due to the significant decrease in tidal volume and to the decline in respiratory rate both pre- and post-vagotomy. Expiratory apnoea of mean duration of 10.0+/-3.4 s was present in the vagally intact rats only. Bilateral midcervical section of the vagus nerve precluded the occurrence of apnoea. Prolongation of the expiratory time (T(E morphine) / T(E control)), which amounted to 10.7+/-2.2-fold in the intact state, was apparently reduced to 1.5+/-0.3-fold after division of the vagi. Morphine significantly decreased mean arterial pressure (MAP) at 30 s after the challenge, the effect persisted for not less than 1 minute and was absent in vagotomized rats. The respiratory changes evoked by morphine reverted to the control level after intravenous injection of naloxone at a dose of 1 mg/kg. Results of this study indicate that opioid receptors on vagal afferents are responsible for the occurrence of apnoea and hypotension evoked by morphine.     

Effect of morphine on breathing and behavior in fetal sheep

To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs

Respiratory muscle blood flow and organ blood flow during endotoxic shock were studied in spontaneously breathing dogs (SB, n = 6) and mechanically ventilated dogs (MV, n = 5) with radiolabeled microspheres. Shock was produced by a 5-min intravenous injection of Escherichia coli endotoxin (0.55:B5, Difco, 10 mg/kg) suspended in saline. Mean arterial blood pressure and cardiac output in the SB group dropped to 59 and 45% of control values, respectively. There was a similar reduction in arterial blood pressure and cardiac output in the MV group. Total respiratory muscle blood flow in the SB group increased significantly from the control value of 51 +/- 4 ml/min (mean +/- SE) to 101 +/- 22 ml/min at 60 min of shock. In the MV group, respiratory muscle perfusion fell from control values of 43 +/- 12 ml/min to 25 +/- 3 ml/min at 60 min of shock. In the SB group, 8.8% of the cardiac output was received by the respiratory muscle during shock in comparison with 1.9% in the MV group. In both groups of dogs, blood flow to most organs was compromised during shock; however, blood flow to the brain, gut, and skeletal muscles was higher in the MV group than in the SB group. Thus by mechanical ventilation a fraction of the cardiac output used by the working respiratory muscles can be made available for perfusion of other organs during endotoxic shock.     

Nonperipheral chemoreceptor stimulation of ventilation by cyanide.

To assess the ventilatory responses elicited by changes of tissue hypoxia, sodium cyanide (0.12 mg/kg-min for 10 min) was infused into the upper abdominal aorta of anesthetized dogs. These infusions produced decreases in oxygen consumption, increases in arterial lactate concentration, and increases in arterial lactate/pyruvate ratio. Coincident with these metabolic changes of hypoxia, minute ventilation (VE) increased 228 +/- SE 36% and arterial PCO2 decreased 21 +/- SE 2 mmHg; therefore, pH increased both in arterial blood in and cisternal cerebrospinal fluid. Following infusion of cyanide into the abdominal aorta, small quantities of cyanide (48 +/- SE 14 mumol/liter) appeared in carotid arterial blood. To evaluate the possibility that the observed increases in VE were due to stimulation of peripheral arterial chemoreceptors by the recirculating cyanide, the carotid and aortic chemoreceptors were denervated in four dogs. Nonetheless, after intra-aortic infusion of sodium cyanide (1.2 mg/kg), ventilation in these chemodenervated animals again increased considerably (154 +/- SE 36%). In order to explore the possibility that cyanide infusion can stimulate ventilation by an extracranial mechanism, heads of vagotomized dogs (including the carotid bodies) were perfused entirely by donor dogs. The intra-aortic infusion of sodium cyanide (0.9 mg/kg) into these head-perfused animals still caused large increases in VE (163 +/- SE 19%). It is concluded that intra-aortic cyanide infusions stimulate VE by an extracranial mechanism other than the carotid and aortic chemoreceptors.     

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.     

Seasonal changes in the cardiorespiratory responses to hypercarbia and temperature in the bullfrog, Rana catesbeiana

We assessed the seasonal variations in the effects of hypercarbia (3 or 5% inspired CO2) on cardiorespiratory responses in the bullfrog Rana catesbeiana at different temperatures (10, 20 and 30 degrees C). We measured breathing frequency, blood gases, acid-base status, hematocrit, heart rate, blood pressure and oxygen consumption. At 20 and 30 degrees C, the rate of oxygen consumption had a tendency to be lowest during winter and highest during summer. Hypercarbia-induced changes in breathing frequency were proportional to body temperature during summer and spring, but not during winter (20 and 30 degrees C). Moreover, during winter, the effects of CO2 on breathing frequency at 30 degrees C were smaller than during summer and spring. These facts indicate a decreased ventilatory sensitivity during winter. PaO2 and pHa showed no significant change during the year, but PaCO2 was almost twice as high during winter than in summer and spring, indicating increased plasma bicarbonate levels. The hematocrit values showed no significant changes induced by temperature, hypercarbia or season, indicating that the oxygen carrying capacity of blood is kept constant throughout the year. Decreased body temperature was accompanied by a reduction in heart rate during all four seasons, and a reduction in blood pressure during summer and spring. Blood pressure was higher during winter than during any other seasons whereas no seasonal change was observed in heart rate. This may indicate that peripheral resistance and/or stroke volume may be elevated during this season. Taken together, these results suggest that the decreased ventilatory sensitivity to hypercarbia during winter occurs while cardiovascular parameters are kept constant.