Organ blood flow and cardiac contractility in anaesthetized cats at 5 bar (500 kPa) ambient pressure

Previous in vivo and in vitro experiments have demonstrated increased cardiac contractility and increased total myocardial blood flow (Qmyocardial) when rats were exposed to normoxic 5-bar (500 kPa) ambient pressure. In the present study, regional blood flow was measured using the microsphere method on nine anaesthetized cats at surface and normoxic 5-bar (500 kPa) ambient pressure. Left ventricular pressure (LVP) and cardiac contractility, measured as peak left ventricular +dP/dt and -dP/dt were measured in six of the cats. Arterial pressure, heart rate and cardiac output remained unchanged after compression, but total Qmyocardial increased by 29% (P less than 0.01) and cerebral blood flow increased by 66% (P less than 0.05). At the same time +dP/dt and -dP/dt was increased by 83% and 102%, respectively (P less than 0.01), while LVP was enhanced by 14% (P less than 0.05). Except for a moderate decrease in partial pressure of oxygen, acid base status in arterial blood remained unchanged. The results indicate that the effects of increased ambient pressure on the heart are general physiological phenomena, which are not only limited to the laboratory rat.     

Cardiovascular responses in paraplegic subjects during arm exercise

The purpose of this study was to examine cardiovascular responses during arm exercise in paraplegics compared to a well-matched control group. A group of 11 male paraplegics (P) with complete spinal cord-lesions between T6 and T12 and 11 male control subjects (C), matched for physical activity, sport participation and age performed maximal arm-cranking exercise and submaximal exercise at 20%, 40% and 60% of the maximal load for each individual. Cardiac output (Qc) was determined by the CO2 rebreathing method. Maximal oxygen uptake was significantly lower and maximal heart rate (fc) was significantly higher in P compared to C. At the same oxygen uptakes no significant differences were observed in Qc between P and C; however, stroke volume (SV) was significantly lower and fc significantly higher in P than in C. The lower SV in P could be explained by an impaired redistribution of blood and, therefore, a reduced ventricular filling pressure, due to pooling of venous blood caused by inactivity of the skeletal muscle pump in the legs and lack of sympathetic vasoconstriction below the lesion. In conclusion, in P maximal performance appears to have been limited by a smaller active muscle mass and a lower SV despite the higher fc,max. During submaximal exercise, however, this lower SV was compensated for by a higher fc and, thus at the same submaximal oxygen uptake, Qc was similar to that in the control group.     

Involvement of nitrogen oxide in the cerebral vasoconstriction during respiration with high pressure oxygen

High pressure oxygen evokes a cerebral vasoconstriction and diminishes cerebral blood flow with the aid of mechanisms which are not yet sufficiently studied. We were checking a hypothesis that the hyperbaric oxygen (HBO2) inactivates cerebral nitrogen oxide (NO), interrupts its basal relaxing effect, and evokes a vasoconstriction. In our experiments, HBO2 decreased cerebral blood flow depending on the pressure. Inhibiting the NO-synthase weakened basal vasorelaxation in breathing with atmosphere air and eliminated the vasoconstriction in exposure to the HBO2. Inactivation of O2 prevented the HBO2-induced vasoconstriction. The data obtained reveal that diminishing of cerebral blood flow in HBO is related to the NO inactivation and weakening of its basal vasorelaxing effect. Possible mechanisms of the NO inactivation may involve its reaction with oxygen and superoxide anion which lead to diminishing of the tissue NO concentration and weakening of its vasorelaxing effect.     

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.     

Hyperoxic vasoconstriction in the brain is realized by inactivation of nitric oxide by superoxide anions

We tested a hypothesis that the cerebral blood flow (CBF) is reduced at hyperbaric oxygen due to inactivation of nitric oxide (NO) by superoxide anions (O2). In our experiments, the CBF was measured under hyperbaric oxygenation (HBO) 4ATA after inhibition of NO synthesis and inactivation of O2. The CBF was reduced at HBO exposure. Inhibition of NO--synthase type I and III (NOS) by L-NAME in the air caused the same decreasing of the CBF as at 4 ATA HBO. Hyperbaric vasoconstriction was diminished after NOS inhibition. Intravenous injection of superoxide dismutase (CuZn SOD) increased the CBF in the air and HBO exposure. This effect disappeared at preliminary NOS inhibition. These data suggest that inactivation of NO by O2 is a more effective mechanism of HBO vasoconstriction.     

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338-342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37-42 Torr, arterial CO2 tension (PaCO2) = 25-30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19-22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7-10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.     

Catheter position and blood gases during constant-flow ventilation

We studied the effect of catheter position and flow rate on gas exchange during constant-flow ventilation (CFV) in eight anesthetized, paralyzed dogs. The distal tips of the insufflation catheters were positioned 0.5, 2.0, 3.5, and 5.0 cm from the tracheal carina. Flow rates were varied between 10 and 55 l/min and steady-state arterial blood gases were measured. At a given flow rate, arterial CO2 pressure (PaCO2) decreased as CFV was administered further into the lung up to a distance of 3.5 cm from the carina; there were no significant differences in PaCO2 at 3.5 and 5.0 cm. For a given catheter position, PaCO2 decreased with increasing flow rate up to a flow rate of 40 l/min. Further increases in flow rate had no significant effect on PaCO2. Arterial O2 pressure (PaO2) was relatively constant at all flow rates and catheter positions. We conclude that, up to a point, CO2 elimination can be improved by positioning the catheters further into the lung; advancing the catheters further than 3.5 cm from the carina may cause over-ventilation of specific lung regions resulting in a relative plateau in CO2 elimination and relatively constant PaO2's. Positioning the catheters further into the lung permits the use of lower flow rates, thus potentially minimizing the risk of barotrauma.     

Ventrolateral medullary surface blood flow determined by hydrogen clearance

The H2 clearance technique was used to determine the blood flow of the postulated respiratory chemosensitive areas near the ventrolateral surface of the medulla. In 12 pentobarbital sodium-anesthetized cats, flow (mean +/- SD) was measured from 25-micron Teflon-coated platinum wire electrodes implanted to a depth of 0.3-0.7 mm. Flow (in ml X min-1 X 100 g-1, n = 35) was 52.8 +/- 28.5 in hypocapnia [arterial CO2 partial pressure (PaCO2) = 21.8 +/- 1.6 Torr], 57.8 +/- 27.5 in normocapnia (PaCO2 = 31.9 +/- 2.2 Torr), and 75.0 +/- 31.7 in hypercapnia (PaCO2 = 44.5 +/- 3.0 Torr). Flow determined from 15 electrodes in adjacent pyramidal tracts (white matter) was less at all levels of CO2; 22.9 +/- 12.3 in hypocapnia, 29.1 +/- 15.9 in normocapnia, and 33.9 +/- 13.9 in hypercapnia. In hypoxia [arterial O2 partial pressure (PaO2) = 39.9 +/- 6.3 Torr] ventrolateral surface flow rose to 87.9 +/- 47.6, and adjacent white matter flow was 35.8 +/- 15.6. These results indicate that flow in the postulated central chemoreceptor areas exceeds that of white matter and is sensitive to variations in PaCO2 and PaO2.     

Ventilatory and blood gas dynamics at onset and offset of exercise in the pony

The purpose of these experiments was to examine the temporal pattern of arterial carbon dioxide tension (PaCO2) to assess the relationship between alveolar ventilation (VA) and CO2 return to the lung at the onset and offset of submaximal treadmill exercise. Five healthy ponies exercised for 8 min at two work rates: 50 m/min 6% grade and 70 m/min 12% grade. PaCO2 decreased (P less than 0.05) below resting values within 1 min after commencement of exercise at both work rates and reached a nadir at 90 s. PaCO2 decreased maximally by 2.5 and 3.5 Torr at the low and moderate rate, respectively. After the nadir, PaCO2 increased across time during both work rates and reached values that were not significantly different (P greater than 0.05) from rest at minute 4 of exercise. Partial pressure of O2 in arterial blood and arterial pH reflected hyperventilation during the first 3 min of exercise. At the termination of exercise PaCO2 increased (1.5 Torr) above rest (P less than 0.05), reaching a zenith at 2-3 min of recovery. These data suggest that VA and CO2 flow to the lung are not tightly matched at the onset and offset of exercise in the pony and thus challenges the traditional concept of blood gas homeostasis during muscular exercise.     

Effect of tracheal bias flow on gas exchange during high-frequency chest percussion

High-frequency chest percussion (HFP) with constant fresh gas flow (VBF) at the tracheal carina is a variant of high-frequency ventilation (HFV) previously shown to be effective with extremely low tracheal oscillatory volumes (approximately 0.1 ml/kg). We studied the effects of VBF on gas exchange during HFP. In eight anesthetized and paralyzed dogs we measured arterial and alveolar partial pressures of CO2 (PaCO2) and O2 (PaO2) during total body vibration at a frequency of 30 Hz, amplitude of 0.17 +/- 0.019 cm, and tidal volume of 1.56 +/- 0.58 ml. VBF was incrementally varied from 0.1 to 1.2 l.kg-1.min-1. At low flows (0.1-0.4 l.kg-1.min-1), gas exchange was strongly dependent on flow rate but became essentially flow independent with higher VBF (i.e., hyperbolic pattern). At VBF greater than 0.4 l.kg-1.min-1, hyperventilatory blood gas levels were consistently sustained (i.e., PaCO2 less than 20 Torr, PaO2 greater than 90 Torr). The resistance to CO2 transport of the airways was 1.785 +/- 0.657 l-1.kg.min and was independent of VBF. The alveolar-arterial difference of O2 was also independent of the flow. In four of five additional dogs studied as a control group, where constant flow of O2 was used without oscillations, the pattern of PaCO2 vs. VBF was also hyperbolic but at substantially higher levels of PaCO2. It is concluded that, in the range of VBF used, intraairway gas exchange was limited by the 30-Hz vibration. The fresh gas flow was important only to maintain near atmospheric conditions at the tracheal carina.     

Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.     

Fetal breathing is not initiated after cord occlusion in the unanaesthetized fetal lamb in utero.

We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2.     

Hyperbaric oxygne tolerance in newborn mammals-hypothesis on mechanisms and outcome

Newborn mammals, compared to adults, are extremely resistant to the CNS effects of hyperbaric oxygenation (HBO) induced by excessive generation of reactive oxygen species. This tolerance to HBO may be related to either physiological responses or the chemical characteristics of the immature brain, including a low cerebral blood flow and energy metabolism and a low concentration of polyunsaturated fatty acids. In adult mammals the main protective mechanism against CNS oxygen toxicity, besides endogenous antioxidants, is a transient HBO-induced cerebral vasoconstriction. How cerebral vasculature reacts to HBO in the immature brain is not known. We present indirect evidence suggesting that HBO in newborn rats induces a persistent cerebral vasoconstriction concurrently with a severe and maintained reduction in ventilation. It is speculated that the outcome of these physiologic responses to hyperoxic exposures may be: (a) extension of tolerance to both CNS and pulmonary oxygen poisoning; (b) creation of a profound hypoxic-ischemic condition in vulnerable neural structures: and (c) impairement of the circulatory and ventilatory responses to hypoxic stimuli on return to air consequent development of a secondary hypoxic-ischemic condition. These hypothetical pre- and post-HBO events may set the stage for the development of some delayed neurological disorders, including the retinopathy of prematurity and the retardation of brain development in fetuses or prematurely-born infants subjected to oxygen therapy.     

Cardiopulmonary control during exercise in the duck

To determine the importance of nonhumoral drives to exercise hyperpnea in birds, we exercised adult White Pekin ducks on a treadmill (3 degrees incline) at 1.44 km X h-1 for 15 min during unidirectional artificial ventilation. Intrapulmonary gas concentrations and arterial blood gases could be regulated with this ventilation procedure while allowing ventilatory effort to be measured during both rest and exercise. Ducks were ventilated with gases containing either 4.0 or 5.0% CO2 in 19% O2 (balance N2) at a flow rate of 12 l X min-1. At that flow rate, arterial CO2 partial pressure (PaCO2) could be maintained within +/- 2 Torr of resting values throughout exercise. Arterial O2 partial pressure did not change significantly with exercise. Heart rate, mean arterial blood pressure, and mean right ventricular pressure increased significantly during exercise. On the average, minute ventilation (used as an indicator of the output from the central nervous system) increased approximately 400% over resting levels because of an increase in both tidal volume and respiratory frequency. CO2-sensitivity curves were obtained for each bird during rest. If the CO2 sensitivity remained unchanged during exercise, then the observed 1.5 Torr increase in PaCO2 during exercise would account for only about 6% of the total increase in ventilation over resting levels. During exercise, arterial [H+] increased approximately 4 nmol X l-1; this increase could account for about 18% of the total rise in ventilation. We conclude that only a minor component of the exercise hyperpnea in birds can be accounted for by a humoral mechanism; other factors, possibly from muscle afferents, appear responsible for most of the hyperpnea observed in the running duck.     

Arterial-alveolar CO2 equilibration in exercising dogs during prolonged rebreathing

Arterial-alveolar equilibration of CO2 during exercise was studied by normoxic CO2 rebreathing in six dogs prepared with a chronic tracheostomy and exteriorized carotid loop and trained to run on a treadmill. In 153 simultaneous measurements of PCO2 in arterial blood (PaCO2) and end-tidal gas (PE'CO2) obtained in 46 rebreathing periods at three levels of mild-to-moderate steady-state exercise, the mean PCO2 difference (PaCO2-PE'CO2) was -1.0 +/- 1.0 (SD) Torr and was not related to O2 uptake or to the level of PaCO2 (30-68 Torr). The small negative PaCO2-PE'CO2 is attributed to the lung-to-carotid artery transit time delay which must be taken into account when both PaCO2 and PE'CO2 are continuously rising during rebreathing (average rate 0.22 Torr/s). Assuming that blood-gas equilibrium for CO2 was complete, a lung-to-carotid artery circulation time of 4.6 s accounts for the observed uncorrected PaCO2-PE'CO2 of -1.0 Torr. The results are interpreted to indicate that in rebreathing equilibrium PCO2 in arterial blood and alveolar gas are essentially identical. This conclusion is at variance with previous studies in exercising humans during rebreathing but is in full agreement with our recent findings in resting dogs.     

Arterial carbon dioxide partial pressure influences CYP4A distribution in the rat brain

PaCO(2) is an important factor in the regulation of cerebral circulation, and it is often used to reduce intracranial pressure through hyperventilation during neurosurgery. Changes in concentration can cause changes in CBF (cerebral blood flow). 20-HETE is a product of CYP4A-mediated AA (arachidonic acid) metabolism and is a powerful endogenous vasoconstrictor; however, its effect on cerebral vasoconstriction in cats, dogs and rats remains to be confirmed. It is known that changes in PaCO(2) can influence the expression of CYP4A in the rat brain, demonstrating the important role of 20-HETE in the mechanism of CO(2)-mediated cerebrovascular reactivity. Thirty healthy adult male Wistar rats that weighed between 200 g and 250 g were randomly divided into three groups (A, B, and C; n=10): group A, normocapnia (PaCO(2) was maintained at approximately 40-45 mmHg); group B, hypocapnia (PaCO(2) was maintained at approximately 20-25 mmHg); and group C, hypercapnia (PaCO(2) was maintained at approximately 60-65 mmHg). Physiological parameters, including HR (heart rate), MBP(mean blood pressure), PH and PaCO(2) were recorded every 30 min, and there were no significant hemodynamic or body temperature differences. The head was removed after 3.5 h to investigate brain CYP4A by immunohistochemistry. Relative to group A, group B exhibited the following changes: an increased pH, decreased PaCO(2), and increased brain CYP4A protein expression (P<0.05). In contrast, group C exhibited decreased PH, increased PaCO(2) and decreased CYP4A protein expression (P<0.05). CO(2) can decrease the expression of brain CYP4A during hypercapnia and increase its expression during hypocapnia.     

Ventilatory responses to increased blood flow and decreased lung volume in awake dogs

The effect of decreased lung volume on ventilatory responses to arteriovenous fistula-induced increased cardiac output was studied in four chronic awake dogs. Lung volume decreases were imposed by application of continuous negative-pressure breathing of -10 cmH2O to the trachea. The animals were surgically prepared with chronic tracheostomy, indwelling carotid artery catheter, and bilateral arteriovenous femoral shunts. Control arteriovenous blood flow was 0.5 l/min, and test flow level was 2.0 l/min. Arterial blood CO2 tension (PaCO2) was continuously monitored using an indwelling Teflon membrane mass spectrometer catheter, and inhaled CO2 was given to maintain isocapnia throughout. Increased fistula flow alone led to a mean 52% increase in cardiac output (CO), whereas mean systemic arterial blood pressure (Psa) fell 4% (P less than 0.01). Negative-pressure breathing alone raised Psa by 3% (P less than 0.005) without a significant change in CO. Expired minute ventilation (VE) increased by 27% (P less than 0.005) from control in both of these conditions separately. Combined increased flow and negative pressure led to a 50% increase in CO and 56% increase in VE (P less than 0.0025) without any significant change in Psa. Effects of decreased lung volume and increased CO appeared to be additive with respect to ventilation and to occur under conditions of constant PaCO2 and Psa. Because both decreased lung volume and increased CO occur during normal exercise, these results suggest that mechanisms other than chemical regulation may play an important role in the control of breathing and contribute new insights into the isocapnic exercise hyperpnea phenomenon.     

Apparent diffusion limitations on branchial CO2 transfer are revealed by severe experimental anaemia in brown bullhead (Ameiurus nebulosus)

In this study, the rapid (within 2 h) effects of acute anaemia on blood gas and acid-base status, as well as cardiorespiratory variables, were examined in brown bullhead (Ameiurus nebulosus). Anaemia was induced by blood withdrawal coupled to volume replacement with saline. Lowering haematocrit from the control value of 23.5+/-1.0% (mean+/-S.E.M.; N=37) to 5.9+/-0.3% (N=37) resulted in a significant increase (by 2.63+/-0.51 torr; N=7) in arterial CO(2) tension (PaCO(2)) over the subsequent 2-h period in the absence of a change in arterial O(2) tension (PaO(2)). Treatment with bovine carbonic anhydrase (CA) reduced the extent of the PaCO(2) increase to the point where it was not statistically significant. In both control and CA-treated fish, arterial pH decreased during acute anaemia; the acidosis was of mixed respiratory and metabolic origin in control fish and primarily metabolic in CA-treated fish. Inducing anaemia caused increases in both cardiac output (V*b) and heart rate that were similar in control and CA-treated fish. Experimental elevation of V*b equivalent to that observed during anaemia, but in the absence of lowered haematocrit, increased PaCO(2) significantly by 1.49+/-0.74 to 1.64+/-0.78 torr (N=5) without affecting PaO(2). These findings suggest that CO(2) excretion in bullhead, as in rainbow trout, is effectively diffusion-limited, and that approximately half of the increase in PaCO(2) measured during the initial 2 h of anaemia results from the impact of increased blood flow (hence decreased gill transit time) in a diffusion-limited system.     

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.     

Microvascular pressures during hypoxia in isolated lungs of newborn rabbits

The purpose of this study was to determine the sites of hypoxic vasoconstriction in lungs of newborn rabbits. We isolated and perfused with blood the lungs from 19 rabbit pups, 7-23 days old. We maintained blood flow constant, continuously monitored pulmonary arterial and left atrial pressures, and alternated ventilation of the lungs with 95% O2-5% CO2 (control), and 95% N2-5% CO2 (hypoxia). Using micropipettes and a servonulling device, we measured pressures in 20-60-micron-diam subpleural arterioles and venules during control and hypoxic conditions. We inflated the lungs to a constant airway pressure of 5-7 cmH2O and kept left atrial pressure greater than airway pressure (zone 3) during micropuncture. In eight lungs we measured microvascular pressures first during control and then during hypoxia. We reversed this order in four lungs. In seven lungs we measured microvascular pressures only during hypoxia. We found a significant increase in pulmonary arterial pressure with no change in microvascular pressures. These results indicate that the site of hypoxic vasoconstriction in lungs of newborn rabbits is arteries greater than 60 micron in diameter.