The role of arterial oxygen tension in the respiratory response to localized heating of the hypothalamus and to hyperthermia

1. Rectal temperatures, respiratory rates, arterial blood gas tensions, arterial pH and the percentage of red cells in arterial blood have been measured in the unanaesthetized ox in a cool environment (15/12 degrees C, dry bulb/wet bulb [DB/WB]), in a hot, dry environment (40/21 degrees C, DB/WB), during hyperthermia, during infra-red irradiation, and during localized heating of the anterior hypothalamus. In some experiments the gas tensions and pH of mixed venous blood, and the percentage saturation of the arterial blood with oxygen, were also measured.2. In the cool environment at a mean rectal temperature (T(r)) of 38.8 degrees C and a respiratory rate (f) of 28/min the mean values obtained from six animals were: arterial oxygen tension (P(a, O) (2)), 93 mm Hg; arterial carbon dioxide tension (P(a, CO) (2)) 42 mm Hg; arterial pH 7.49; arterial oxygen saturation (S(a, O) (2)) 94%; arterial oxygen capacity (Cap(a, O) (2)) 13.6 vol.%; arterial packed cell volume (P.C.V.) 29%.3. Exposure to the hot, dry environment resulted in a small increase in the rectal temperature and thermal polypnoea, but there were no statistically significant changes in the blood gas tensions.4. During hyperthermia statistically significant increases occurred in rectal temperature, respiratory rate, P(a, O) (2), pH and arterial haematocrit, while the P(a, CO) (2) decreased. The venous oxygen tension (P(v, O) (2)) decreased also, and the tentative conclusion was made that although the oxygenation of arterial blood remained unimpaired during hyperthermia, tissue hypoxia may supervene. At very high levels of deep body temperature, some evidence for a secondary decrease in P(a, O) (2) was obtained.5. Localized heating of the anterior hypothalamus caused an increase in respiratory rate and in P(a, O) (2). The P(v, O) (2) increased also. These changes were considered to be due to increased cardiac output and diversion of blood to the skin.6. During infra-red irradiation of three animals at an environmental temperature of 40/21 degrees C, the respiratory rate increased, but the P(a, O) (2) decreased.     

Sudden infant death syndrome: a preconditioning approach to acute arterial hypoxemia

The blood hemoglobin F (HbF) concentration increases in response to chronic arterial hypoxemia and is abnormally elevated in sudden infant death syndrome (SIDS) post-mortem indicating a need for greater oxygen affinity of hemoglobin (Hb) or diminished oxygen usage by tissues or both.Modifying Hb oxygen affinity in rats revealed that increased, rather than decreased, hemoglobin-oxygen affinity permitted survival at greatly reduced environmental oxygen pressures equivalent to high altitude. Decreased Hb-oxygen affinity resulted in bradycardia 5-10 minutes before death. Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home demonstrated cardiovascular failure with hypotension and bradycardia, rather than a cessation of breathing.A fall in blood pressure and acidosis due to hypoxemia in combination with reduced arterial oxygen saturation leads to circulatory failure, heart failure and death.It is speculated that the final mechanism of SIDS mimics failure to survive at high altitudes and very low environmental oxygen pressures when low arterial oxygen pressures combine with decreased Hb-oxygen affinity lead to severe hypoxemia and death.     

Effect of an allosteric modifier of hemoglobin, RSR-4, on oxygen affinity and oxygen saturation of hemoglobin in rabbits

Theoretically, if the arterial partial oxygen pressure (PaO2) does not change, a right shift in the oxygen equilibrium curve (OEC) of hemoglobin should reduce arterial oxygen saturation. In this study we investigate whether a right shift in the OEC of hemoglobin decreases transcutaneous oxygen saturation (Tc-SO2) following the administration of an allosteric effector, 2-[4-(((3, 5-dichloroanilino)-carbonyl) methyl) phenoxy]-2-methylpropionic acid (RSR-4). The effect of RSR-4 on hemoglobin oxygen affinity was studied in four New Zealand white male rabbits. Following intraperitoneal administration of RSR-4, Tc-SO2 decreased in a dose-dependent manner. P50 (partial oxygen pressure at 50% hemoglobin oxygen saturation) in whole blood increased as the concentration of RSR-4 increased. Tc-SO2 decreased as whole-blood affinity (1/P50) decreased. There was no positive correlation between Tc-SO2 and PaO2. We concluded that a decrease in hemoglobin oxygen affinity following RSR-4 administration reduced arterial oxygen saturation. This decrease in the presence of an allosteric effector such as RSR-4 in vivo can be detected and monitored as a reduction in Tc-SO2.     

The effect of hypoxia, hypercapnia and hypotension upon carotid body blood flow and oxygen consumption in the cat

1. Carotid body blood flow (c.b.f.), the arterio-venous oxygen (A-V O(2)) difference and oxygen consumption were measured in forty-seven cats, anaesthetized with pentobarbitone, paralysed with gallamine and ventilated artificially. Carotid sinus and cervical sympathetic nerves were intact throughout.2. A system for perfusing the carotid body artificially with blood is described and evidence is given which shows that similar results were obtained whether the carotid body was naturally or artificially perfused.3. With arterial pressure, blood gas tensions and pH within physiological limits, c.b.f. varied between 33 and 68 mul./min, average 41.5; A-V O(2) difference between 0.21 and 0.46 ml./100 ml., average 0.34, and calculated oxygen consumption between 0.115 and 0.195 mul. O(2)/min, average 0.147.4. With constant mean arterial pressure, hypoxia (30-40 mm Hg P(a, O2)) or hypercapnia (> 50 mm Hg P(a, CO2)) resulted in a small increase of c.b.f., up to 14 mul./min above control; an average fall of A-V O(2) difference by 49% of control and an average fall of oxygen consumption by 36% of control.5. Carotid body blood flow fell linearly with mean arterial pressure over the range 100-170 mm Hg, the slope of the curve varying between 0.78 and 1.22 mul. min(-1). mm Hg(-1). M.A.P. A-V O(2) difference was unaffected so that oxygen consumption fell in proportion to c.b.f.6. It is concluded that the unique response of the carotid body to these stimuli is a fall in oxygen consumption and that this bears a closer relation to the known pattern of chemoreceptor discharge than do changes in total blood flow.     

Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis.

We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of "physiologic" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures.     

Respiratory and circulatory effects of breathing 100% oxygen in the new-born lamb before and after denervation of the carotid chemoreceptors

1. Methods are described for measuring tidal volume and frequency, end-tidal CO(2), blood pressure and heart rate, and arterial gas tensions in the unanaesthetized new-born lamb.2. The resting values of minute ventilation (V)/kg body wt. and arterial oxygen and carbon dioxide tension, (P(a, o2)) and (P(a, CO2)) were similar to those which have been reported in the new-born baby. There was a direct and significant relation between P(a, o2) and P(a, CO2) and the age of the lamb.3. Thirty-five unanaesthetized lambs aged 40 min to 10 days breathed 100% oxygen; minute ventilation fell by an average of 19% of control, end-tidal CO(2) increased and the ratio of change in tidal volume (DeltaV(T)) to change in pressure (DeltaP) (DeltaV(T)/DeltaP) remained constant. In a proportion of lambs, a small decrease in blood pressure and heart rate was observed. The effect of breathing 100% O(2) on lung compliance was variable.4. These changes in ventilation were virtually abolished after both sinus nerves had been cut.5. The results therefore suggest that a significant hypoxic drive to ventilation exists in the new-born lamb and that this drive is mediated by functioning and mature peripheral chemoreceptors.6. Preliminary evidence suggested that, on 100% O(2), the sensitivity of new-born lambs to inhaled CO(2) was reduced.     

Physiological responses to prolonged aquatic hypoxia in the Queensland lungfish Neoceratodus forsteri

The effects of moderate and severe hypoxia on air breathing frequency and respiratory properties of the blood of the Queensland (Australian) lungfish Neoceratodus forsteri were measured in fish exposed to these conditions for 14-22 days at 20 degrees C. Haemoglobin oxygen affinity increased after exposure to moderate hypoxia (PW(O(2)) = 60 mmHg), but did not increase further after exposure to severe hypoxia (PW(O(2)) = 40 mmHg). The P(50) of whole blood (20 degrees C, P(CO(2)) = 16.0 mmHg) fell from 22.0 +/- 1.5 mmHg in normoxic conditions to 19.0 +/- 1.0 mmHg in hypoxic conditions. Under both moderate and severe hypoxia, haematocrit, haemoglobin, blood lactate, and erythrocyte phosphate concentrations did not differ from normoxic values. The observed increase in haemoglobin oxygen affinity in response to aquatic hypoxia is typical of compensatory responses seen in obligate water breathers, but smaller. This suggests that the capacity of lungfish to respond to hypoxia by breathing air removes the necessity for further left-shifting of the oxygen equilibrium curve.     

The relationship of oxygen transport and cardiac index for the prevention of sickle cell crises

The formation of deoxyhemoglobin S (deoxy-Hb S) polymers is the key triggering event for the complex pathophysiologic manifestations of sickle cell anemia (SCA). This polymer formation is associated with a marked right-shifted oxyhemoglobin dissociation curve (decreased affinity, increased P50), which results in a decrease in arterial oxygen saturation (SaO2. There is a delay period ("delay time") from the formation of deoxy-Hb S to polymerization that is markedly sensitive (to the power of 30-40) to the concentration and solubility changes of deoxy-Hb S. Deoxy-Hb S polymer formation leads to sickle cell vaso-occlusion, a unique characteristic of SCA. This theoretical study, which views SCA as a disease of oxygen transport, provides a novel framework to suggest that a small to modest increase in cardiac index (by decreasing the P50 and thus increasing the SaO2) could change the distribution of the delay times (sec) such that the balance between occlusion and opening of microcirculatory vessels is shifted favoring the opening of these vessels, therefore disfavoring vaso-occlusion. Our approach integrates a mathematical model of oxygen transport in SCA with: (1) the expression relating the solubility of deoxy-Hb S to SaO2, and (2) the kinetic expression relating the delay time to the solubility of deoxy-Hb S.     

The role of the cervical sympathetic nerve in the regulation of oxygen consumption of the carotid body of the cat

1. Carotid body blood flow (c.b.f.) and carotid arterial-carotid body venous oxygen (A-V O(2)) difference were measured and carotid body oxygen consumption calculated in twenty-six cats anaesthetized with pentobarbitone sodium, paralysed with gallamine triethiodide and ventilated mechanically.2. With the sinus nerves intact and with blood gas tensions and carotid sinus pressure within physiological limits, section of either the pre- or post-ganglionic cervical sympathetic nerve on the same side caused an average rise in c.b.f. of 9.2 mul./min, in A-V O(2) difference of 0.09 ml./100 ml. and in carotid body oxygen consumption of 0.075 mul./min.3. When the pre- or post-ganglionic cervical sympathetic nerves were stimulated, c.b.f. and A-V O(2) difference fell. The fall in c.b.f. was enhanced at high P(a, CO2); the fall in A-V O(2) difference and in calculated oxygen consumption was enhanced at low mean arterial pressure (M.A.P.) or P(a, O2).4. Following sympathectomy, a reduction of M.A.P. at constant P(a, O2) and P(a, CO2) caused a fall in c.b.f. and a commensurate rise in A-V O(2) difference so that carotid body oxygen consumption remained approximately constant.5. When P(a, O2) was altered over the range 35 to > 400 mm Hg, or P(a, CO2) over the range 27-70 mm Hg at constant M.A.P., c.b.f. changed by amounts which were similar to those observed when the sympathetic nerves were intact and A-V O(2) difference changed in the opposite direction so that carotid body oxygen consumption similarly remained constant.6. Comparison of these results with those observed when the sympathetic nerves were intact indicates that the sympathetic nerves exert a vasoconstrictor effect upon carotid body blood vessels over a wide range of blood gas tensions and arterial pressure and that they also tend to diminish the rate of carotid body oxygen consumption. The mechanisms which may be involved in this regulation are discussed.     

Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons.

Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.     

Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans

The aim of this study was to test our hypothesis that both phasic cardiac vagal activity and tonic pulmonary vagal activity, estimated as respiratory sinus arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to improve the efficiency of pulmonary gas exchange in humans. We examined the effect of blocking vagal nerve activity with atropine on pulmonary gas exchange. Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and respiratory frequency through a respiratory circuit with a respiratory analyser. Arterial partial pressure of O(2) (P(aO(2))) and arterial oxygen saturation (S(pO(2))) were measured, and alveolar-to-arterial P(O(2)) difference (D(A-aO(2))) was calculated. Anatomical dead space (V(D,an)), alveolar dead space (V(D,alv)) and the ratio of physiological dead space to tidal volume (V(D,phys)/V(T)) were measured. Electrocardiogram was recorded, and the amplitude of R-R interval variability in the high-frequency component (RRIHF) was utilized as an index of RSA magnitude. These parameters of pulmonary function were measured before and after administration of atropine (0.02 mg kg(-1)). Decreased RRIHF (P < 0.01) was accompanied by decreases in P(aO(2)) and S(pO(2)) (P < 0.05 and P < 0.01, respectively) and an increase in D(A-aO(2)) (P < 0.05). Anatomical dead space, V(D,alv) and V(D,phys)/V(T) increased (P < 0.01, P < 0.05 and P < 0.01, respectively) after atropine administration. The blockade of the vagal nerve with atropine resulted in an increase in V(D,an) and V(D,alv) and a deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our findings suggest that both phasic cardiac and tonic pulmonary vagal nerve activity contribute to improve the efficiency of pulmonary gas exchange in hypoxic conscious humans.     

Oxygen saturation regularity analysis in the diagnosis of obstructive sleep apnea

OBJECTIVE: The present study assessed the validity of approximate entropy (ApEn) analysis of arterial oxygen saturation (SaO(2)) data obtained from pulse oximetric recordings as a diagnostic test for obstructive sleep apnea (OSA) in patients clinically suspected of suffering this disease. METHODOLOGY: A sample of 187 referred outpatients, clinically suspected of having OSA, was studied using nocturnal pulse oximetric recording performed simultaneously with complete polysomnography. ApEn analysis was applied to SaO(2) data. RESULTS: Patients with OSA presented significantly higher approximate entropy levels than those without OSA (1.08+/-0.30 versus 0.47+/-0.26). Apnea-hypopnea index was correlated significantly with ApEn (r=0.607; p<0.001). Using receiver operating characteristic curve analysis, we obtained a diagnostic sensitivity of 88.3% and specificity of 82.9%, positive predictive value of 88.3% and a negative predictive value of 82.9%, at a threshold of 0.679. As a diagnostic test, this method presents high sensitivity and specificity compared to traditional methods in the diagnosis of OSA. CONCLUSION: We conclude that ApEn analysis of SaO(2) data obtained from pulse oximetric recordings could be useful as a diagnostic technique for OSA subjects.     

Evaluation of a new reflectance pulse oximeter for clinical applications

The design of a noninvasive reflectance pulse oximeter that uses the same principle of transmittance pulse oximeter and analyses the oxygen saturation of arterial blood was described. Four sets of red and infra-red LEDs were used as light sources. The respective reflectance photoelectric outputs were used to make an internal calibration curve of the instrument relative to the arterial oxygen saturation values measured with a Co-Oximeter (OSM-3) in five healthy nonsmoking subjects during steady-state hypoxaemia. The accuracy of the present instrument was studied in six patients with respiratory failure. From 22 samples, a good correlation coefficient (0.98) with a standard deviation of 1.42 was obtained in the range between 73 and 100 per cent between the arterial oxygen saturation measured with the present instrument and that with the Co-Oximeter. The result strongly suggests the usefulness of this oximeter in monitoring patients with hypoxaemia.     

Intravascular inhomogeneous oxygen distribution in microvessels: theory

Cross-sectional oxygen distribution in microvessels in most previous studies has been assumed to be homogeneous. Recent studies using phosphorescence quenching microscopy or microspectrophotometry showed a decline in oxygen profile near the arterial wall. In this study we performed theoretical analysis of intravascular P(O(2)) and S(O(2)) profiles in arterioles by using a radial diffusion model with a constant oxygen efflux from the vascular lumen, taking intravascular flow distribution into account. Theoretical calculations indicated that radial oxygen diffusion and a laminar flow pattern would create inhomogeneous intravascular oxygen profile with a decline toward the arterial wall. As mean blood flow velocity became lower, the difference between the centerline oxygen level and the inner surface level became larger. In conclusion, it is suggested that oxygen efflux from the vascular lumen and less convective supply near the vascular wall create a decline in P(O(2)) as well as S(O(2)) toward the arterial wall.     

Preoxygenation and pulse oximetry may delay detection of esophageal intubation

A case of delayed detection of esophageal intubation is described. Preoxygenation and pulse oximetry were used, and the first indication of tube misplacement was arterial desaturation indicated by the pulse oximeter. The combination of preoxygenation and pulse oximetry may contribute to delays in early detection of endotracheal tube misplacement for the following reasons: (1) preoxygenation results in a pulmonary reservoir of oxygen sufficient to maintain arterial hemoglobin saturation for an extended period of time; and (2) the maintenance of normal arterial saturations for an extended period after inadvertent esophageal tube placement may lead the practitioner to initially seek other causes of declining oxygen saturations. Although pulse oximetry is an acknowledged advance in patient monitoring, it must not be utilized as an early indication of correct endotracheal tube placement.     

Blood oxygen affinity and alveolar ventilation in relation in body weight in mammals.

The validity of the concept relating blood oxygen affinity and alveolar ventilation to body weight in homeothermic mammals was reexamined with blood pH used as the fixed variable. Blood Po2 at 50% saturation at pH 7.4 (P50(7.4)) and PCO2 of oxygenated blood at pH 7.4 (PCO2(7.4)) from a variety of homeothermic mammals were determined at 37 degrees C by in vitro equilibration techniques. In some species, arterial PCO2, PO2, and pH were also measured. PCO2(7.4), which was similar to arterial PCO2, showed a correlation coefficient of +0.33 with body weight over the range of 28-100,000 g and +0.90 among the species under 200 g. P50(7.4) values, which ranged from 26.0 to 38.7 mmHg for all the species, were not well correlated (r = -0.43) with body weight. For the small mammals (less than 200 g) the correlation coefficient was -0.91. In vivo P50 at the body temperature and arterial pH, although different from P50(7.4), showed a similar correlation with body weight. The lack of valid generalization suggests that body weight is only one of the composite factors that influence O2 transport systems.     

Modulation of perfusion and oxygenation by red blood cell oxygen affinity during acute anemia

Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O(2)) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5-hydroxymethyl-2-furfural (5HMF) were used to decrease and increase Hb-O(2) affinity. In vitro P50s (partial pressure of O(2) at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD), and microvascular Po(2) levels were measured. RBcs with P50 of 45 mm Hg increased tissue Po(2) and decreased O(2) delivery (Do(2)) and extraction (Vo(2)) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue Po(2), Do(2) and Vo(2). Erythrocytes with increased Hb-O(2) affinity maintained hemodynamic conditions, Do(2) and decreased tissue Po(2). This study shows that in an anemic condition, maximal tissue Po(2) does not correspond to maximal Do(2) and Vo(2).     

Estimation of arterial PCO2 from a lung model during ramp exercise in healthy young subjects

The aim of this study is to propose a new approach to estimate non-invasively arterial carbon dioxide partial pressure (P(a)CO2) approach was based on the reconstruction of alveolar gas composition over each breath from a tidally ventilated lung model (P(M)(CO2)). Eight healthy young subjects were studied during a ramp exercise test on a cycle ergometer. Arterial samples were drawn at rest and every minute during the exercise test for determination of P(a)CO2 . P(a)CO2 was compared with indirect estimates of P(CO2) : P(M)(CO2), end-tidal P(CO2) (P(ET)(CO2)) and an empirical equation involving P(ET)(CO2) and tidal volume (P(J)(CO2)). The difference between estimated and measured P(a)CO2 on the whole ramp exercise was -0.3+/-1.9mmHg for P(M)(CO2), 1.0+/-2.2mmHg for P(ET)(CO2) and -1.7+/-1.7mmHg for P(J)(CO2) . P(ET)(CO2) and P(J)(CO2) were significantly different from actual P(a)CO2 (P<0.001). It is concluded that, on the basis of the bias, the breathing lung model gave better estimates of P(a)CO2 than the two other indirect methods during ramp exercise.     

Insufficient ventilation as a cause of impaired pulmonary gas exchange during submaximal exercise

Pulmonary ventilation and gas exchange were determined during prolonged skiing (approximately 76% of V(O2, max); cardiac output=26-27 L min(-1)) using diagonal technique (DIA) for 40 min followed by 10 min of double poling (DPOL) and 10 min of leg skiing (LEG). Exercise caused approximately 2-5% reduction of arterial oxygen saturation Sa(O2). For a given cardiac output and V(O2), DPOL presented higher V(E), lower Pa(CO2) and a more efficient pulmonary gas exchange, revealed by higher PA(O2) and Pa(O2) and lower A-aD(O2). The A-aD(O2) widened 2 mmHg L(-1) of cardiac output increase. However, for a given cardiac output and V(O2), exercise mode had an important influence on pulmonary ventilation and gas exchange. Highly trained cross-country skiers' present about 2 units reduction in Sa(O2) from resting values during submaximal exercise at 76% of V(O2, max). Half of the reduction in saturation is accounted for by the rightward-shift of the oxygen dissociation curve of the haemoglobin. The exercise duration has almost no repercussion on pulmonary gas exchange in these athletes, with the small effect on Sa(O2) associated to the increase in body core temperature.     

A dual control system for assisting respiration

A dual control system for assisting respiration was developed. The following features were included: (i) ventilation is controlled by the metabolic rate from continuously measured CO₂ output, (ii) physiologic dead space approximated as a linear function of tidal volume is used to estimate alveolar ventilation, and (iii) oxygen concentration in the inspired gas is regulated by the arterial oxygen saturation continuously measured with an ear oximeter. The ventilator was used on dogs with an inspired gas mixture of 85% N₂ and 15% O₂. Arterial P_co2 was maintained between 36 and 39 mmHg for a duration exceeding 60 minutes. Although an oscillatory variation was seen in the arterial P_o2 due to the adoption of an on-off control mode to regulate the O₂ fraction in the inspired gas, it remained between 80 and 136 mmHg. The dual control system of assisting respiration is capable of maintaining both the arterial P_co2 and P_o2 within normal levels at any level of metabolic rate and any respiratory frequency.