Reduction In PCO2 Research Articles

The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end‐expiratory pressure during air and CO2 inhalation

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO2 inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO2 inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO2 (PaCO2) when breathing air. With increasing fraction of CO2 in the inspiratory gas, the difference in PaCO2 between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post-expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO2 is markedly reduced.

Severe Reduction in End-Tidal PCO2 following Unilateral Pulmonary Artery Occlusion in a Child with Pulmonary Hypertension

Department of Anesthesiology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands and Department of Anest Kesiology, University Hospital Leiden, Leiden, The Netherlands. Address correspondence to Dr. Schuller, Department of Anesthesiology, University of Amsterdam, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Accepted for publication January 17, 1989.

Anesthetic effects on liver and muscle glycogen concentrations: rest and postexercise.

We compared the effects of three different anesthetics (halothane, ketamine-xylazine, and diethyl ether) on arterial blood gases, acid-base status, and tissue glycogen concentrations in rats subjected to 20 min of rest or treadmill exercise (10% grade, 28 m/min). Results demonstrated that exercise produced significant increases in arterial lactate concentrations along with reductions in arterial Pco2 (PaCO2) and bicarbonate concentrations in all rats compared with resting values. Furthermore, exercise produced significant reductions in the glycogen concentrations in the liver and soleus and plantaris muscles, whereas the glycogen concentrations found in the diaphragm and white gastrocnemius muscles were similar to those found at rest. Rats that received halothane and ketamine-xylazine anesthesia demonstrated an increase in Paco2 and a respiratory acidosis compared with rats that received either anesthesia. These differences in arterial blood gases and acid-base status did not appear to have any effect on tissue glycogen concentrations, because the glycogen contents found in liver and different skeletal muscles were similar to one another cross all three anesthetic groups. These data suggest that even though halothane and ketamine-xylazine anesthesia will produce a significant amount of ventilatory depression in the rat, both anesthetics may be used in studies where changes in tissue glycogen concentrations are being measured and where adequate general anesthesia is required.

Podogenic columnar calcite from the Oolite Group (Lower Carboniferous), South Wales

Calcrete palaeosols in the Oolite Group have microspar hardpan layers overlying clay-rich nodular layers which, in turn, overlie the degraded host oolite. Within and immediately below hardpan layers there are extensive sheet-like and fan developments of columnar calcite with individual crystals up to 30 cm long. Crystals range from those with straight extinction and normal growth zonation through feathery crystals to those showing sweeping extinction. The calcretes accumulated within a seasonal climate with hardpan accumulation probably occurring through evaporation during the dry season. The columnar calcite precipitated from more dilute solutions with maximum growth probably occurring during the wet season. Precipitation may have been partly or wholly bacterially mediated, or induced by the reduction in pco2 of fluids as they migrated out of the extremely restricted microporosity of the hardpan. Columnar fabrics reflect low supersaturations relative to those at which the hardpan accreted, inhibition of crystal nucleation and of growth on x-axis parallel faces, and an excess of CO22− availability over Ca2+. Growth and nucleation may have been inhibited by the presence of particular organic compounds or clays. The range in crystal form is related to the degree of poisoning of crystal growth faces by organic compounds.

Transient hyperoxia and cerebral blood flow velocity in infants born prematurely and at full term.

Little is known about the effects of hyperoxia on the cerebral circulation of human infants. Using duplex Doppler we measured the changes in cerebral blood flow velocity in a group of full term (n = 15) and premature infants (n = 17, median gestational age 31 weeks) in response to a transient threefold increase in oxygen tension. Measurements of blood gas tensions as well as blood pressure and cerebral blood flow velocity were made over a period of 20 minutes on three occasions for each infant; during normal oxygenation, hyperoxia, and normal oxygenation. There was a fall in cerebral blood flow velocity in 15 of the 17 premature infants with hyperoxia and the median reduction was 0.06 cm/second for every 1 kPa increase in oxygen tension. There was no significant change in either PCO2 or blood pressure during the period of hyperoxia. The cerebral blood flow velocity fell in all 15 infants born at full term during hyperoxia, but there was a simultaneous and significant reduction in PCO2 at the same time as the hyperoxia. Analysis of variance suggested that in the infants born at full term the change in carbon dioxide had most effect in the reduction of cerebral blood flow velocity, rather than the hyperoxia itself. We conclude that in premature infants, cerebral vascular resistance may be altered by a fall in cerebral blood flow velocity in the presence of hyperoxia.

Physiological Responses of the Rock Crab Cancer irroratus (Say) to Environmental Hyperoxia. I. Acid-Base Regulation

Hemolymph acid-base and ion levels and acidic equivalent exchange with the experimental water were monitored in rock crabs (Cancer irroratus Say) exposed to control normoxia (PIo2 ≃ 150 torr), 48 h of hyperoxia (Po2 ≃ 512 torr), and 24 h of subsequent normoxic recovery. Hemolymph CO₂ binding was assessed in vitro on oxygenated and deoxygenated samples. Settled normoxic crabs had the following acid-base status: pH—8.01; Pco2—2.1 torr, and [HCO₃⁻]-9.3 meq·liter⁻¹ and appeared to be in proton balance with the experimental water. Within 6 h of exposure to hyperoxia, the hemolymph exhibited a significant acidosis (0.15 pH units) that was due to respiratory CO2 (Pco2 increased by 50%). This acid-base imbalance was restored between 6 and 24 h by a 50% increase in [HCO₃⁻]. This coincided with a 13-fold increase in excretion of acidic equivalents (primarily titratable) into the experimental water that continued for up to 10 h. Numerically, there was excellent correspondence between acid efflux and the magnitude of the extracellular proton load. Although crabs continued to hypoventilate, preexperimental Pco2 was reestablished by 24 h, suggesting that the original hypercapnia had been due to a perfusion limitation. Between 24 and 48 h, circulating [HCO₃⁻] was also restored to resting levels accompanied by an equivalent net base excretion into the bathing medium. When normoxia was reinstated, hemolymph exhibited a reduction in Pco2 plus a further reduction in [HCO₃⁻] at constant Pco2, making pH alkalotic. The base efflux that persisted into the recovery period significantly exceeded that required to restore extracellular acid-base balance. It is suggested that this base load originated intracellularly and that the reduced cardiac output during hyperoxia limited its removal into the hemolymph. Circulating lactate exhibited a similar washout effect during recovery. Hemolymph of C. irroratus had a low nonbicarbonate buffer value (β) corresponding to reduced protein concentration. However, the Haldane effect, which theoretically could account for the release of 2.13 mmol CO2 per mmol O2 bound, was larger than observed in other decapods.

Effects of PCO2, pH and extracellular calcium on contraction of airway smooth muscle from rats

The effect of changes in PCO2 on airway smooth muscle was studied in acetylcholine-induced contractions of isolated rat trachea. Elevation of superfusate PCO2, 38 mm Hg (pH 7.49), to 168 mm Hg (pH 6.74) decreased tension to 68% of control tension; reduction of PCO2 to 19 mm Hg (pH 7.84) increased tension to 104%. Similar effects on tension occurred when pH was altered by varying superfusate bicarbonate concentration at constant PCO2. Modification of the response to changes in PCO2 by varying extracellular calcium (Ca2+) concentration and also by verapamil indicated that changes in PCO2 and pH may alter Ca2+ uptake by the smooth muscle. Calcium uptake was measured by 45Ca2+ and the lanthanum method. At control pH 7.49, net Ca2+ uptake was 5.34 mmol Ca2+/kg trachea 60 min after the onset of contraction; this decreased to 4.26 at pH 6.88, and increased to 6.58 at pH 7.85. The results suggest that the mechanism whereby chages in PCO2 affect airway smooth muscle contraction is a pH-dependent alteration of Ca2+ uptake.

Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats.

The dose effect of caffeine (10-70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.

Cellular mechanism of force development in cat middle cerebral artery by reduced PCO2.

These studies were undertaken to determine the effect of reducing a PCO2 below physiological levels on cat middle cerebral artery. Upon reduction of PCO2 from 37 to 14 torr (pH 7.4) we observed membrane depolarization and force development. Reducing PCO2 decreased the slope of the Em vs. log [K]o curve and increased the slope of the steady-state I/V relationship suggesting that the change in Em was due to reduction of outward K+ conductance (gk). Elevation of pH from 7.37 to 7.6 had a very similar effect on these cerebral arterial muscle cells, depolarizing the muscle membrane (reducing the Em vs. log [K]o curve) and increasing the slope of the I/V relationship to statistically equivalent values as reduction of PCO2. Returning PCO2 from 14 to 37 torr rapidly relaxed these preparations, but only transiently. This relaxation was followed by a rebound contraction within 3 min, demonstrating a transient nature for the action of elevating PCO2 in cerebral arteries. The response to changing pHo followed a slower time course but did not change with time. These studies demonstrate that both elevated pHo and reduced PCO2 activate cerebral arterial muscle by a mechanism which includes reduction in gk. However, it can not be determined if these similar responses and reduction of gk are mediated by changing pHi or mediated through different mechanisms. It is possible that pHo and PCO2 can modify cerebral arterial tone by direct mechanisms and not necessarily by their effect on pHi. It is clear, however, that reduction of PCO2 and elevation of pHo both activate cerebral arterial muscle by a mechanism which includes reduction of gk.

Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis.

Recent classifications of the several pathophysiologic types of distal renal tubular acidosis (secretory, voltage dependent, and gradient) have been based on the response of acidification parameters to a series of provocative maneuvers in vivo and in vitro. A reduction in the difference in urine and blood CO2 tension during bicarbonate loading (U-B pCO2 gradient), a widely applied parameter, has been employed as an index of reduced distal nephron proton secretion. This study was designed to test the validity of the U-B pCO2 gradient in a variety of experimental models of distal renal tubular acidosis by measuring and comparing disequilibrium pH (a direct technique to detect H+ secretion in situ) with the pCO2 in the papillary collecting duct of the rat in vivo during bicarbonate loading. Chronic amiloride, lithium chloride, and amphotericin-B administration, and the post-obstructed kidney models were employed. Amiloride resulted in an acidification defect which did not respond to sulfate infusion (urine pH = 6.15 +/- 0.08), and was associated with an obliteration of the acid disequilibrium pH (-0.26 +/- 0.05- -0.08 +/- 0.03) and reduction in papillary pCO2 (116.9 +/- 3.2 - 66.9 +/- 2.5 mmHg). The defect induced by lithium administration responded to Na2SO4 (urine pH = 5.21 +/- 0.06) but was similar to amiloride with respect to the observed reduction in disequilibrium pH (-0.04 +/- 0.02) and pCO2 (90.3 +/- 3.0 mmHg). The post-obstructed kidney model was characterized by an abnormally alkaline urine pH unresponsive to sulfate (6.59 +/- 0.06) and a reduction in disequilibrium pH (+0.02 +/- 0.06) and pCO2 (77.6 +/- 3.6 mmHg). Amphotericin-B resulted in a gradient defect as characterized by excretion of an acid urine after infusion of sodium sulfate (5.13 +/- 0.06). Unlike other models, however, amphotericin-B was associated with a significant acid disequilibrium pH (-0.11 +/- 0.05) and an appropriately elevated urine pCO2 (119.8 +/- 6.4 mmHg) which did not differ from the respective values in control rats. Thus, these findings support the use of the U-B pCO2 as a reliable means of demonstrating impaired distal nephron proton secretion in secretory and voltage-dependent forms of distal renal tubular acidosis (RTA) and supports the view that proton secretion is not impaired in gradient forms of distal RTA.

Rectal aminophylline in the management of apnoea of prematurity.

Rectal suppositories as an alternative to intravenous aminophylline in the management of recurrent apnoea were studied in 41 preterm infants of mean gestation 28.3 weeks and mean birthweight 1176 g. Therapeutic blood concentrations were obtained two hours after a rectal loading dose of 10 mg/kg, with steady concentrations and maximum reduction in apnoeic episodes (from a mean of 0.5 per hour to 0.09 per hour) within 24 hours on a maintenance dose of 10 mg/kg/day. There was good correlation between the rectal dose and the plasma theophylline concentration. Several infants showed a significant reduction in Pco2 when treated with aminophylline. Side effects were related to the plasma theophylline concentration and were not seen at concentrations less than 14 mg/l.

Medullary collecting duct acidification. Effects of potassium, HCO3 concentration, and pCO2.

The medullary collecting duct (MCD) from renal outer medulla possesses significant HCO3 absorptive capacity. In vitro microperfusion studies have shown that HCO3 absorption in this segment is carbonic anhydrase dependent, affected by peritubular and luminal chloride concentrations, is independent of the presence of Na or the presence of Na transport, and is stimulated by mineralocorticoid hormone. The present in vitro microperfusion studies defined regulatory influences on MCD acidification as assessed by acute changes in the extracellular K and HCO3 concentrations and pCO2. These studies showed that acute changes in the peritubular K concentration to either 0 mM K or 50 mM K have no significant effect on HCO3 absorption in MCD. Intracellular voltage recordings showed that elevation of peritubular K concentration from 5 to 50 mM produced only a 2.8 mV depolarization of the basolateral cell membrane of MCD cells. In addition, acute reduction of peritubular K from 5 to 0 mM had no significant effect on intracellular voltage. Studies that were designed to assess the effects of HCO3 concentration and pCO2 on acidification showed that acute reduction of peritubular HCO3 concentration from 25 to 5 mM (pH change from 7.4 to 6.8) increased lumen-positive voltage from 30.2 +/- 3.8 to 40.0 +/- 4.4 mV, and simultaneously increased net HCO3 absorption from 15.6 +/- 1.9 to 22.9 +/- 2.9 pmol X mm-1 X min-1. Elevation of peritubular HCO3 concentration from 25 to 50 mM (pH change from 7.4 to 7.8) significantly decreased lumen-positive voltage from 33.8 +/- 2.4 to 26.7 +/- 1.5 mV and simultaneously decreased net HCO3 absorption from 17.9 +/- 1.2 to 12.8 +/- 1.3 pmol X mm-1 X min-1. In addition, acute reduction of peritubular pCO2 from 40 to less than 14 mmHg (final pH 7.8-7.9) significantly decreased lumen-positive voltage from 31 +/- 4.4 to 15.7 +/- 1.0 mV. Coincidentally, HCO3 absorption decreased significantly from 11.0 +/- 3.7 to 5.3 +/- 0.7 pmol X mm-1 X min-1. We conclude that: alteration of peritubular K concentration from 0 to 50 mM in vitro does not affect HCO3 absorption in the MCD, and that this lack of effect appears to be related to a low basolateral cell membrane K conductance; net HCO3 absorption and the associated lumen-positive voltage can be modulated by in vitro changes in peritubular HCO3 and pCO2 (or pH); and the MCD perfused in vitro appears to be a good model for studying the mechanisms and regulation of distal nephron acidification.

Aminophylline Reduces Cerebral Blood Flow Velocity in Low-Birth-Weight Infants

Cerebral blood flow decreases substantially in the adult after a single bolus injection of aminophylline. To determine if the cerebral circulation of the low-birth-weight infant behaves in a similar manner, we measured cerebral blood flow velocity (CBFV) in the anterior cerebral arteries of nine infants treated with an intravenous bolus dose of 5 mg/kg of body weight of aminophylline. A reduction in CBFV of 21% and 17% was observed at 60 and 120 minutes following the aminophylline administration. There was a concurrent substantial reduction in PCO2 from 45 +/- 7 to 39 +/- 7 mm Hg before and 120 minutes after the aminophylline administration, respectively. The reduction in CBFV may be the result of a reduction in PCO2 resulting from aminophylline treatment.

Relationship between hematocrit and CO2 contents in whole blood and true plasma.

The amount of CO2 liberated out of the red cell was measured by decreasing PCO2 in human blood with different fractional hematocrits of about 0.24, 0.45, and 0.75, respectively, in order to elucidate whether it depends on the hematocrit and the intracellular pH. From a venous PCO2 level the PCO2 of the sample blood was lowered to 12 Torr. PCO2, CO2 content, pH, Cl-, and Na+ were measured in whole blood and true plasma before and after the reduction of PCO2. Change in water concentration in plasma was calculated from change in plasma Na+ concentration. The bicarbonate shift well counterbalanced to the Cl- shift. As the hematocrit was decreased, the amount of CO2 released per mol of hemoglobin increased, while the change in intracellular bound CO2 concentration decreased. That is, the intracellular bound CO2 became higher in the lower hematocrit blood than in the higher hematocrit one. This fact suggested that the intracellular pH became higher as the hematocrit was lowered, and thus the amount of alkali bound with hemoglobin or the CO2 release was enhanced. The Donnan ratio of the bound CO2 at 12 Torr was independent of the hematocrit, though the pH was inversely related to the hematocrit.

Evaluation of lyophilized heparin syringes for the collection of arterial blood for acid base analysis.

The effects of liquid heparin on the analysis of acid/base status of arterial blood include a reduction in PCO2 and an increase in PO2. A study was performed to compare a lyophilised heparin syringe with a liquid heparin glass syringe for collection of blood for acid/base analysis. No significant difference between the variables measured in blood taken in the two syringes was demonstrated.

Arterial and Mixed Venous Blood Gas Tensions in Exercising Ducks

Adult White Pekin ducks were exercised at three work levels on a treadmill at speeds of .9, 1.47, and 2.16 km/hr for 20 min with a 90 min rest period following each exercise period. Blood gas and pH analyses were performed on samples simultaneously withdrawn from the brachial artery and the right ventricle (as an estimate of mixed venous blood) at predetermined intervals during the experiment. Both arterial and mixed venous PCO2 significantly decreased with the increases in the level of exercise. Arterial pH did not change significantly from resting values at any level of exercise. Mixed venous pH decreased at the onset of exercise but returned to near resting value by the end of each exercise period. These measurements indicate that ducks increase their ventilation during exercise above that required to eliminate the generated CO2. Because the increased ventilation produces a reduction in arterial PCO2, it is unlikely that peripheral or central CO2-sensitive chemoreceptors are responsible for the ventilatory drive.

Renal metabolic rate during changes in bicarbonate-dependent sodium reabsorption in the proximal tubules

Previous studies indicate that water and at least 2 mol NaCl are reabsorbed in the proximal tubules for each mol NaHCO3 reabsorbed. To examine the effect on cortical energy metabolism of variations in this bicarbonate-dependent sodium reabsorption, the cortical metabolic rate was examined in anaesthetized dogs by the heat production technique during continuous infusion of saline and ethacrynic acid. Sodium reabsorption was altered either by intravenous infusion of a large dose of acetazolamide (500 mg/kg body wt) or by changing plasma P CO2 during metabolic alkalosis. Acetazolamide reduced bicarbonate reabsorption by 71 ± 2%, sodium reabsorption by 54 ± 2% and cortical heat production by 21 ± 3%. A rise in PCO2 to 16.4 ± 1.3 kPa during metabolic alkalosis increased sodium reabsorption by 25 ± 3% and cortical heat production by 14± 2%. A similar elevation of plasma PCO2 during metabolic acidosis had no effect on electrolyte reabsorption or the cortical metabolic rate. A reduction in PCO2 to 2.3 ± 0.3 kPa reduced sodium reabsorption by 40 ± 3% and cortical heat production by 19 ± 2%. We conclude that a rise in proximal tubular reabsorption requires energy. However, the changes in energy requirement are small, accounting for previous failures to observe significant changes in cortical energy metabolism during less extensive changes of sodium reabsorption in the proximal tubules.

Metabolic Alkalosis Complicating Weaning From Mechanical Ventilation

Metabolic alkalosis was identified and confirmed as a precipitator of acute hypercapnea. As a result, weaning from mechanical ventilator therapy was delayed. Correction of alkalosis followed by reduction of PCO2 confirmed the compensatory mechanism during alkalosis, and weaning from intermittent mandatory ventilation then proceeded at an appropriate rate.

Renal metabolic rate during changes in bicarbonate-dependent sodium reabsorption in the proximal tubules.

Previous studies indicate that water and at least 2 mol NaCl are reabsorbed in the proximal tubules for each mol NaHCO3 reabsorbed. To examine the effect on cortical energy metabolism of variations in this bicarbonate-dependent sodium reabsorption, the cortical metabolic rate was examined in anaesthetized dogs by the heat production technique during continuous infusion of saline and ethacrynic acid. Sodium reabsorption was altered either by intravenous infusion of a large dose of acetazolamide (500 mg/kg body wt) or by changing plasma Pco2 during metabolic alkalosis. Acetazolamide reduced bicarbonate reabsorption by 71 +/- 2%, sodium reabsorption by 54 +/- 2% and cortical heat production by 21 +/- 3%. A rise in Pco2 to 16.4 +/- 1.3 kPa during metabolic alkalosis increased sodium reabsorption by 25 +/- 3% and cortical heat production by 14 +/- 2%. A similar elevation of plasma Pco2 during metabolic acidosis had no effect on electrolyte reabsorption or the cortical metabolic rate. A reduction in Pco2 to 2.3 +/- 0.3 kPa reduced sodium reabsorption by 40 +/- 3% and cortical heat production by 19 +/- 2%. We conclude that a rise in proximal tubular reabsorption requires energy. However, the changes in energy requirement are small, accounting for previous failures to observe significant changes in cortical energy metabolism during less extensive changes of sodium reabsorption in the proximal tubules.

A STUDY OF NALOXONE AND DOXAPRAM AS AGENTS FOR THE REVERSAL OF NEUROLEPTANALGESIC RESPIRATORY DEPRESSION IN THE CONSCIOUS RABBIT

The effectiveness of naloxone and doxapram in reversing the respiratory depressant actions of fentanyl and droperidol in the rabbit has been examined. Both drugs did not reverse fully the depression of respiratory frequency produced by the neuroleptanalgesic agents. Doxapram also failed to reverse fully the depression of minute volume produced by fentanyl and droperidol, although naloxone was adequate in this respect. However, analysis of arterialized venous blood showed that both naloxone and doxapram not only prevented the increase in PCO2 caused by fentanyl and droperidol, but caused also a significant decrease. A reduction in PCO2 was seen also when either naloxone or doxapram was given to untreated rabbits. With doxapram this appeared to be a result of pure respiratory stimulation. Naloxone also produced a reduction in standard bicarbonate.