Haldane Effect Research Articles

Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease

To compare data derived from a computer model of the pulmonary circulation with data from a case series of patients with chronic obstructive pulmonary disease (COPD). To evaluate the specific factors contributing to CO2 retention due to oxygen therapy in patients with acute exacerbations of COPD. Data from a computer model of the pulmonary circulation were compared with a previous case series. Patient data were derived from previous case series. Simulated application of oxygen therapy. The computer model of the pulmonary circulation generates data comparable with those data from a series of patients with COPD treated with supplemental oxygen and permits identification of the causes for hypercarbia. Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and modulates the Haldane effect, resulting in changes in physiologic deadspace. Changes in physiologic deadspace are sufficient to account for the hypercarbia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.

The interaction between oxygen and carbon dioxide movements in fishes

Abstract Many teleost fishes have haemoglobins which possess a Root effect, a large Haldane effect and a low buffer capacity. This combination of characteristics influences the interaction between movements of oxygen and carbon dioxide in the red cell, in the respiratory epithelium, and in the tissues. The presence of the Root effect may limit oxygen uptake at the gills due to an accumulation of Bohr protons released upon oxygenation. However, the Root effect is probably important in maintaining or elevating blood PO 2 during muscle capillary transit, enhancing oxygen delivery to the tissues. Bohr protons are reversibly bound to haemoglobin. The release of Bohr protons during oxygenation facilitates bicarbonate dehydration at the gills, while Bohr proton binding facilitates CO 2 hydration at the tissues. In some teleost fishes, most of the Bohr protons are released and bound to haemoglobin, between 50 and 100% of haemoglobin-oxygen saturation (27). This trait is probably significant in maximizing oxygen uptake at the gills and in conserving body CO 2 stores during exposure to hypoxia and exercise, when the lower reaches of the haemoglobin-oxygen equilibrium curve are used.

Haemoglobin function in intact lamprey erythrocytes: interactions with membrane function in the regulation of gas transport and acid-base balance.

Haemoglobin function within lamprey erythrocytes offers a unique solution to gas transport among vertebrates. Lamprey haemoglobin within intact erythrocytes is in oligomer/monomer equilibrium and has an oxygen affinity similar to that of haemoglobin in other active fishes. The cooperativity of oxygen binding, which is reduced at low pH values, the effect of protons and the effect of the concentration of haemoglobin on its oxygen affinity are all due to dissociation/association reactions of the haemoglobin molecules. The permeability of the lamprey red cell membrane to acid and base equivalents is very low, and plasma bicarbonate cannot therefore be dehydrated to carbon dioxide to any significant extent during the residence time of blood in the gills. This potential limitation on carbon dioxide excretion is overcome, however, by the high intraerythrocytic pH and the marked oxygenation-linked pH changes in the erythrocyte, which are due to the large Haldane effect of the haemoglobin. Owing to the relative impermeability of the erythrocyte membrane to acid equivalents, intraerythrocytic haemoglobin cannot take part in the acid-base buffering of the extracellular compartment. As a consequence, extracellular acid loads cause marked fluctuations in plasma pH.

Influence of hypoxic duration and posthypoxic inspired O2 concentration on short term potentiation of breathing in humans.

1. Short term potentiation (STP) of breathing refers to respiratory activity at a higher level than expected just from the dynamics of the peripheral and central chemoreceptors. In humans STP is activated by hypoxic stimulation. 2. To investigate the effects of the duration of hypoxia and the posthypoxic inspired O2 concentration on STP, the ventilatory responses to 30 s and 1, 3 and 5 min of hypoxia (end-tidal PO2, P(ET.O2) approximately 6.5 kPa) followed by normoxia (P(ET.O2) approximately 14.5 kPa) and hyperoxia (P(ET.O2) approximately 70 kPa) were studied in ten healthy subjects. End-tidal PCO2 (P(ET.CO2)) was clamped during hypoxic and recovery periods at 5.7 kPa. 3. Steady-state ventilation (VE) was 13.7 +/- 0.6 l min-1 during normoxia and increased to 15.5 +/- 0.3 l min-1 during hyperoxia (P < 0.05) due to the reduced Haldane effect and some decrease in cerebral blood flow (CBF). 4. The mean responses following hypoxia reached normoxic baseline after 69, 54, 12 and 12 s when 30 s and 1, 3 and 5 min of hypoxia, respectively, were followed by normoxia. An undershoot of 10 and 20% below hyperoxic baseline was observed when 3 and 5 min of hypoxia, respectively, were followed by hyperoxia. Hyperoxic VE reached hyperoxic baseline after 9, 15, 12 and 9 s at the termination of 30 s and 1, 3 and 5 min of hypoxia, respectively. 5. Normoxic recovery from 30 s and 1 min of hypoxia displayed a fast and subsequent slow decrease towards normoxic baseline. The fast component was attributed to the loss of the hypoxic drive at the site of the peripheral chemoreceptors, and the slow component to the decay of the STP that had been activated centrally by the stimulus. A slow decrease at the termination of 30 s and 1 min of hypoxia by hyperoxia was not observed since this component was cancelled by the increase in ventilatory output due to the reduced Haldane effect and some decrease of CBF. 6. Decay of the STP was not apparent in the normoxic recovery from 3 and 5 min of hypoxia as a slow component since it cancelled against the slow ventilatory increase related to the increase of brain tissue PCO2 due to the reduction of CBF at the relief of hypoxia. The undershoot observed when hyperoxia followed 3 and 5 min of hypoxia reflects the stimulatory effects of hyperoxia on VE. 7. The manifestation of the STP as a slow ventilatory decrease depends on the duration of hypoxia and the subsequent inspired oxygen concentration. We argue that STP is not abolished by the central depressive effects of hypoxia, although the manifestation of the STP may be overridden or counteracted by other mechanisms.

HCO 3− dehydration by the blood of an elasmobranch in the absence of a Haldane effect

We measured in vivo arterial P CO 2 and Ca CO 2 in Scyliorhinus canicula and found them to be very low (∼ 1 Torr and 3 mmol 1 −1 respectively). In vitro, the Haldane effect was functionally absent, and there was no detectable β-adrenergic Na +/H + exchange, in contrast to teleosts. The HCO 3 − dehydration rate of the blood, measured by a radioisotopic assay (Wood and Perry, J. Exp. Biol. 157 : 349–366, 1991), was indenpendent of steady-state deoxygenation or oxygenation, unaffected by rapid oxygenation, and insensitive to isoprenaline, amiloride, and removal of urea or TMAO. SITS and acetazolamide reduced the rate; HCO 3 −/Cl − exchange rather than intracellular carbonic anhydrase (CA) was the rate-limiting factor. The rate was not altered by steady-state plasma [HCO 3 −], but increased linearly with P CO 2 and the RBC concentration, saturating at hematocrits ⩾ 15%. The rate in separated plasma accounted for ∼ 50% of the whole blood rate, was higher than in trout plasma or saline, and was inhibited by acetazolamide. The presence of CA in the normally circulating blood plasma of dogfish may contribute to highly effecient CO 2 excretion in vivo.

The conversion of plasma HCO 3 ? to CO2 by rainbow trout red blood cells in vitro: adrenergic inhibition and the influence of oxygenation status

This study employed a recently developed radioisotopic assay (Wood and Perry 1991) to examine the inhibition, induced by catecholamines, of the conversion of plasma HCO 3 (-) to CO2 in acidotic trout blood, and the influence of oxygenation status on the response. Blood was incubated in vitro at PCO 2= 2 torr, and 10(-6) M noradrenaline was employed as the adrenergic stimulus. In particular we investigated whether the inhibition of plasma HCO 3 (-) conversion could be explained by a limited supply of H(+)s for the intracellular HCO 3 (-) dehydration reaction because of competition by the adrenergically activated Na /H(+) exchanger. Hypoxia (PO 2= 15 torr) was employed as a tool to intensify this competition. Hypoxia raised RBC pHi, pHe, and plasma total CO2 concentration (CCO 2) by the Haldane effect, and increased the magnitude of Na(+)/H(+) activation, expressed as the change in the transmembrane pH gradient (pHe-pHi). However hypoxia did not alter the inhibition of the conversion of plasma HCO 3 (-) to CO2 caused by noradrenaline. Hypoxia itself stimulated the RBC-mediated conversion of plasma HCO 3 (-) to CO2 by about 20% in the presence or absence of noradrenaline. The conversion rate was strongly correlated with pHe, pHe-pHi, and plasma CCO 2 in these experiments, but not with pHi. We conclude that adrenergically mediated inhibition in the conversion of plasma HCO 3 (-) to CO2 by trout RBCs is not due to competitive limitation on intracellular H(+)s, but rather to changes in the electrochemical gradient for HCO 3 (-) entry and/or to CO2 recycling from plasma to RBC. The deoxygenated condition helps to promote CO2 excretion at the level of the RBC.

Mitochondrial DNA variation and Haldane's rule in the Papilio glaucus and P. troilus species groups

Variation in mitochondrial DNA (mtDNA) was surveyed, using restriction endonucleases, in all species of the Papilio glaucus and P. troilus groups (Lepidoptera: Papilionidae). Phylogenetic and distance relationships of mtDNA generally confirmed traditional species limits in the two species groups and compared favourably with a prior survey of their allozymes. The most notable exceptions were P. rutulus and P. eurymedon, which share their mtDNA, yet maintain numerous morphological and ecological distinctions in sympatry. In organisms with heterogametic females, like the Lepidoptera, the deficiencies of hybrid females that are expected on the basis of Haldane's rule should lead to congruence of mtDNA variants with species boundaries. In the P. glaucus group, the extent of mtDNA differences between species pairs generally coincided with the extent of the Haldane effect, as well as with the presence of major species differences on sex chromosomes (X effect).

Zero-point fluctuation in quasi one-dimensional antiferromagnets: theory and experiment

A systematic comparison is given of the quantum reduction in the ordered spin of quasi one-dimensional Heisenberg antiferromagnets as predicted by spin-wave theory and as measured in ionic systems with known spin-wave parameters. Simple linear theory yields a leading term (1/(2 pi ))ln(C mod J/J' mod )-1/2 where further terms can be neglected for practical purposes if mod J'/J mod <10-2; such expressions are listed for ferromagnetic and antiferromagnetic square and triangular lattices of antiferromagnetic chains with zero anisotropy. For half-integer-spin systems with 1/2<or=S<or=5/2, excellent agreement with experiment is found over the range 10-2> mod J'/J mod >10-4 when a known correction for 'kinematical interactions' is applied. It should thus be possible to identify covalency reductions in excess of 10%. For the S=1 system CsNiCl3, however, the measured spin reduction may indicate extra quantum fluctuations related to the Haldane effect. From the susceptibility behaviour, the quantum ground state for progressively smaller mod J'/J mod is argued to increasingly resemble a singlet separated from other states by an energy gap.

In vitro Interactions Between Oxygen and Carbon Dioxide Transport in the Blood of the Sea Lamprey (Petromyzon Marinus)

ABSTRACT In vitro experiments were carried out to examine the interactions between oxygen and carbon dioxide transport in the blood of the sea lamprey. Oxygen dissociation curves for whole blood obtained from quiescent lampreys had Hill numbers (NH) ranging from 1.52 to 1.89. The Bohr coefficient for whole blood was −0.17 when extracellular pH (pHe) was considered, but was much greater (−0.63) when red blood cell pH (pHi) was considered. The pHi was largely dependent on haemoglobin oxygen-saturation and the pH gradient across the red blood cell membrane was often reversed when was increased and/or was lowered. The magnitude of the increase in pHi associated with the Haldane effect ranged from 0.169 pH units at 2.9 kPa to 0.453 pH units at a of 0.2 kPa. Deoxygenated red blood cells had a much greater total CO2concentration than oxygenated red blood cells, but the nonbicarbonate buffer value for the red blood cells was unaffected by oxygenation. Plasma was not significantly different under oxygenated or deoxygenated conditions. Partitioning of CO2 carriage in oxygenated and deoxygenated blood supports recent in vivo observations that red blood cell CO2 carriage can account for much of the difference between arterial and venous blood. Together, the results also suggest that oxygen and carbon dioxide transport may not be tightly coupled in the blood of these primitive vertebrates. Finally, red cell sodium concentrations were dependent on oxygen and carbon dioxide tensions in the blood, suggesting that sodium-dependent ion transport processes may contribute to the unique strategy for gas transport in sea lamprey blood.

Quasielastic and Inelastic Neutron Scattering on RbNiCl3

Quasielastic and inelastic neutron scattering experiments on S =1 quasi 1-D Heisenberg antiferromagnet, RbNiCl 3 were performed. The temperature dependence of the spin correlation length suggests a finite 1-D correlation even at T =0 (K). The dispersion relation in the 3-D ordered phase can be well described by the phenomenological theory of a quasi 1-D Heisenberg antiferromagnet including the Haldane effect. Our results support early works on CsNiCl 3 suggesting the influence of the novel quantum effect even in 3-D ordered phase of the quasi 1-D, S =1 Heisenberg antiferromagnet.

Pulmonary gas exchange during intermittent ventilation in the American alligator

The present study characterized pulmonary gas exchange in the American alligator, Alligator mississipiensis during ventilation and apnea at a body temperature (Tb) of 25°C. Pulmonary gas exchange parameters were measured on a breath-by-breath basis utilizing a computer-assisted data acquisition system. In addition, paired blood samples were analyzed from left and right atrium during ventilation and voluntary apneas (1, 2, 5 and 10 min). Measurements of lung P O2 and P CO2 indicated that as apnea progressed, CO 2 flux into the lung decreased rapidly while O 2 was continuously removed at a constant and steady rate. The reduction in V̇ CO2 resulted in a decrease in R (<0.4). Blood gas measurements indicated that the pulmonary arterial-pulmonary venous P CO2 difference, (Ppa-Ppv) CO2 was 4.9 ± 0.9 mmHg during ventilation, decreased and became negative within 2 min of apnea, reaching −3.9 ± 0.6 mmHg after 10 min. It is postulated that during apnea the Haldane effect accounts for both thegas behavior across the lung and insures a continued CO 2 flux into the lung during apnea.

The effect of temperature and hypoxia on the respiratory physiology of the squat lobsters, Munida rugosa and Munida sarsi (anomura, galatheidae)

1. 1. An increase in temperature between 5 and 15C resulted in progressive increases in oxygen consumption ( M o 2 ) and in the rates of heart beat and scaphognathites. Exposure to higher temperatures (20C) was accompanied by a reduction in M o 2 , heart and scaphognathite rates. At these temperatures, the animals appeared to be stressed and prolonged exposure frequently resulted in death. 2. 2. Both M. rugosa and M. sarsi were able to maintain their M o 2 , independent of P o 2 , over a wide range of oxygen tension ( P = 40–55 Torr). During hypoxia, there was a pronounced increase in heart rate and scaphognathite rate but, at oxygen tensions below the P c, both decreased sharply. Neither species was very tolerant of total anoxia; M. rugosa could survive for up to 8 hr, but for M. sarsi, survival was limited to only 4 hr. 3. 3. The oxygen and carbon dioxide transporting properties of the haemolymph were also studied. Values for the in vivo P o 2 , of the pre- and post-branchial haemolymph were 38 ± 9 and 86.2 ± 11 Torr, respectively, in M. rugosa. The oxygen affinity of the haemocyanin of both species was quite low (at 10C and pH 7.8, P 50 = 20.3 and 49.6 Torr in M. rugosa and in M. sarsi, respectively) and exhibited a moderate Bohr effect (θ = −0.43). 4. 4. Oxygen affinity was found to be temperature sensitive (ΔH = − 25.5 and −33.6 kJ/mol in M. rugosa and M. sarsi, respectively) but the magnitude of the Bohr effect did not change significantly with increasing temperature. The haemolymph of both species had a similar buffering capacity ( β = C co 2 / P co 2 =3.4 mmol/l/ Torr) which was also unaffected by temperature. The haemolymph of these species also exhibited a moderate Haldane effect.

Effects of oxygen saturation on the CO2 transport properties of Lampetra red cells.

We investigated the effects of haemoglobin oxygenation on the carbon dioxide transport properties of lamprey (Lampetra fluviatilis) erythrocytes. The non-bicarbonate buffering capacity of deoxygenated lamprey erythrocytes was -43 mmol.L-1.pH unit-1. The carbon dioxide content of oxygenated erythrocytes was 7-8 mM lower than that of deoxygenated erythrocytes over a range of carbon dioxide tensions. This was the result of a pronounced Haldane effect (proton uptake by haemoglobin upon deoxygenation): at extracellular pH 7.5, the intracellular pH of oxygenated erythrocytes was 7.67, and increased to 7.91 when the haemoglobin-oxygen saturation decreased to 7%. No specific oxylabile binding of bicarbonate or carbon dioxide to haemoglobin occurred under the conditions of the present study. Owing to the high red cell pH and its large increase upon deoxygenation, carbon dioxide can be effectively transported in lamprey blood, although plasma bicarbonate is not available for carbon dioxide excretion because of the lack of rapid anion exchange across the red cell membrane.

In Vivo Demonstration of the Haldane Effect during Extracorporeal Gas Exchange

During the extracorporeal support (LFPPV-ECCO2R) of 11 patients suffering from severe lung failure (ARDS), we consistently noticed a higher arterial than mixed-venous PCO2 in blood samples drawn at the same time. Two explanations are possible: a) the Haldane effect (HE), b) CO2 from lung tissue metabolism. In order to distinguish changes in PCO2 due to the HE from those due to tissue CO2 production, CO2 content (CCO2) was calculated. The results were compared to animal experiments with hyperoxic apnea, after which arterial and mixed-venous samples were drawn simultaneously. All blood gas samples were analyzed for pH, PCO2, PO2, and O2-saturation, from which CCO2 was calculated. In both groups, PaCO2 was 2.15 mmHg (2.7 mmHg respectively) higher at a lower CaCO2 (-2.87 ml/l, -14.9 ml/l). Oxygen saturation increased by 8.1% in the human group and 17.8% in the animal group. A significant relationship was found between changes in PCO2 and changes in O2-saturation. This is a demonstration of the Haldane effect.

Measuring the Efficiency of an Artificial Lung: 1. Carbon Dioxide Transfer

The performance of a hollow fibre artificial lung ('Capiox E') was analysed by measurement of the 'parallel deadspace' of the device under varying conditions in 21 patients. The efficiency with which carbon dioxide was exchanged was determined by the time available for equilibration between the blood and gas phases. When this equilibration coefficient was less than 12 seconds per litre of blood flow per litre of gas flow, there was a marked reduction in the efficiency of gas exchange. Under certain conditions, the 'counter-current' design of the device apparently permitted the clearance of carbon dioxide at a partial pressure greater than that which was found in the mixed venous blood. This anomalous behaviour may represent in vivo confirmation of the Haldane effect.

Respiratory properties of the blood of the little penguin Eudyptula minor

1. 1. Oxygen and CO 2 carriage and buffering capacity were studied in blood from little penguins ( Eudyptula minor). 2. 2. Hill plots were linear over a wide range of O 2 saturation, with a Hill coefficient of 3.2. Half saturation pressure (P 50) was 35.1 torr. Fixed acid Bohr effect was low (− 0.39), and mean Haldane effect was 0.34 mol CO 2/(mol O 2). 3. 3. pK' of the bicarbonate buffer system was 6.086. 4. 4. Buffering capacities of whole blood (20.8 mmol/1/pH) and plasma (22.3 mmol/1/pH) were similar to most other birds, but much lower than other penguins. 5. 5. The low non-bicarbonate buffer capacity and high Hill coefficient may act to increase oxygen unloading during dives.

Genetic manipulation for the control of Lymantria dispar

Gene manipulation on the Goldschmidt theory is not likely to be successful in the control of the gypsy moth, Lymantria dispar (L.), because the great excess of males described by Goldschmidt in a particular race cross is not due to sex reversal but to the Haldane effect, and the males in this cross are fully fertile. Genetic engineering holds out most promise for suppression of the moth using a spray containing the baculovirus Autografia califnica ‘engineered’ to contain a hormone gene which causes the pest caterpillar to stop eating. The virus can also be ‘engineered’ to be specific for L. dispar and to destroy itself after it has been used. There are marked racial differences in L. dispar but we have not encountered phenotypic polymorphism such as occurs in Biston betularia L. An advantage could be taken of lack of polymorphism by decreasing atmospheric pollution so as to lighten the bark colour of trees and to render the male gypsy moths on the barks of the trees more visible to predators. In the genus Orgyia, the Japanese female O. thyellina attracts male O. antiqua better than does the female O. antiqua. The relevance of this finding to an improved ‘disparlure’ against L. dispar is discussed.

Blood Respiratory Properties and the Effect of Swimming on Blood Gas Transport in the Leopard Shark Triakis Semifasciata

ABSTRACT Changes in vascular pressures, blood respiratory properties and blood gas transport induced by swimming were investigated in the leopard shark Triakis semifasciata (Girard). In resting sharks, the mean ventral and dorsal aortic pressures (systolic/diastolic) were 6.8/5.6 kPa and 4.5/3.9 kPa, respectively, and only the former were increased significantly during swimming. Swimming also caused a significant decline in venous , (1.6 to 0.9kPa), O2 content (0.9 to 0.4 mmol l−1) and percentage O2 saturation (, 39 to 18%) but the arterial variables were not affected. A significant decline in venous pH and an increase in venous also occurred during swimming but lactate concentration did not increase during or after swimming. An in vivo dissociation curve compiled from blood and data for sharks in the resting, swimming and post-swimming recovery phases shows a mean P50 of 2.04 kPa, as determined by Hill transformation. The pH-bicarbonate plot for this fish shows a weak blood buffer capacity of 9.3 mmol I−1 pH unit−1 and during swimming the average blood pH and bicarbonate concentration follow the buffer line which was not compensated in recovery. Neither oxygenated nor deoxygenated blood pH values were affected by CO2 equilibration, suggesting the absence of a Haldane effect. Thus, at the expense of respiratory acidosis, Triakis can aerobically sustain long (up to 60 min) and moderately intense (0.45 Ls−1, where L is body length) periods of swimming by increasing cardiac output and tapping its venous reserve.

Respiratory pigments: interactions between oxygen and carbon dioxide transport

Oxygen and carbon dioxide are transported in vertebrates and invertebrates by a wide range of respiratory pigments. These respiratory gases are not transported independently of one another, and this review considers the influence of carbon dioxide on oxygen transport and vice versa. A specific effect of carbon dioxide or bicarbonate, decreasing oxygen affinity, is found in many haemoglobins, but the effect is often reduced in the presence of organic phosphates. Clear experimental data are available for mammalian haemoglobins but in birds and lower vertebrates more data are required to verify the presence and magnitude of the CO2 effect. In erythrocruorins and haemocyanins CO2 increases O2 affinity, whereas in haemerythrins, as in haemoglobin, CO2 again decreases oxygen affinity. Much of our knowledge of invertebrate respiratory pigments is based, however, on data from one or two species. A specific effect of CO2 on O2 affinity has also often been found only at high CO2 partial pressures, which may be outside the physiological range for these species. More in vivo experimental data on CO2 values are required for these species, and further studies on other species may help to explain this discrepancy. The interaction of O2 and CO2 transport is mainly through the Haldane effect, i.e., deoxygenated blood having a greater capacity for CO2 than oxygenated blood. This is due directly to the formation of carbamino groups (carbamate) and also to the fact that deoxygenated blood binds relatively more protons than oxygenated blood. This forms the basis for the linkage between the Bohr and Haldane effects. In some species in which the Bohr coefficient is below −1.0, an akalosis in the tissues may be induced. Large Haldane effects may be particularly effective in promoting CO2 unloading when the partial pressure difference of CO2 between arterial and venous blood is small. Carbamate formation may account for 10–20% of the CO2 transported in mammals, but its role in lower vertebrates and invertebrates has only recently been considered. Carbon dioxide transport is modulated by those factors that influence O2 affinity as these in turn influence the Haldane effect.

Arterial and Mixed Venous Blood Gas Status during Apnoea of Intubation — Proof of the Christiansen-Douglas-Haldane Effect in Vivo

The Christiansen-Douglas-Haldane effect, in short the Haldane effect, describes the dependence of the CO2 binding of blood on the degree of oxygenation of haemoglobin. Under the physiological conditions of an 'open' system between blood and alveoli the partial pressure of arterial CO2 (PaCO2), must be less than that of mixed venous blood (PvCO2). During the unphysiological conditions of a 'closed' system, e.g. hyperoxic apnoea, i.e. continuous oxygen uptake without CO2 delivery by the lungs, the PaCO2 will not only approximate the PvCO2 but will even exceed it. Without the Haldane effect, rapid adjustment of PaCO2 to PvCO2 would be expected during apnoea due to the lack of CO2 excretion. If, however, as undertaken in this study, ongoing oxygenation (high alveolar PO2 (PACO2) with concomitant lack of CO2 delivery (apnoea, i.e. the CO2 concentration remains constant) lead to a continuing sufficient oxygenation of blood during its passage through the lung capillaries, then this leads to a rightwards shift of the CO2 binding curve--the Haldane effect. The resulting increase in PCO2 as shown here actually leads to an arterial-mixed venous CO2 partial pressure difference (avDPCO2) of 2.8 +/- 1.8 mmHg. The results described substantiate for the first time the existence of the Haldane effect under clinical conditions.