Raised immunoglobulin A and circulating T follicular helper cells are linked to the development of food allergy in paediatric liver transplant patients.

BACKGROUND: Post-transplant food allergy (LTFA) is increasingly observed after paediatric liver transplantation (LT). Although the immunopathology of LTFA remains unclear, immunoglobulin (Ig) E seems to be implicated. OBJECTIVE: To study humoral and cellular immunity in paediatric LT patients in search for factors associated with LTFA, and compare with healthy controls (HC) and non-transplant food-allergic children (FA). METHODS: We studied serum Ig levels in 29 LTFA, 43 non-food-allergic LT patients (LTnoFA), 21 FA patients and 36 HC. Serum-specific IgA and IgE against common food allergens in LTFA, IgA1 , IgA2 and joining-chain-containing polymeric IgA (pIgA) were measured. Peripheral blood mononuclear cells were analysed by flow cytometry for B and T cell populations of interest. RESULTS: Serum IgA and specific IgA were higher in LTFA compared to LTnoFA. LTFA patients had the highest proportion of circulating T follicular helper cells (cTfh). The percentage of cTfh correlated positively with serum IgA. Unique in LTFA was also the significant increase in serum markers of mucosal IgA and the decrease in the Th17 subset of CXCR5(-) CD4(+) cells compared to HC. Both LT patients exhibited a rise in IgA(+) memory B cells and plasmablasts compared to HC and FA. CONCLUSIONS: LT has an impact on humoral immunity, remarkably in those patients developing FA. The increase in serum markers of mucosal IgA, food allergen-specific IgA and cTfh cells observed in LTFA, point towards a disturbance in intestinal immune homoeostasis in this patient group.

Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma.

BACKGROUND: Myeloid dendritic cells (mDCs) and costimulatory molecules such as ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is known in human allergic disease. The aim of this study was to characterize the phenotype and ICOSL expression of mDCs from allergic rhinitis patients (AR) and their functional correlates on mDC regulation of T cell responses. METHODS: Human blood myeloid, CD1c(+) DCs were isolated from AR or healthy controls. Expression of costimulatory molecules inducible costimulatory ligand (ICOSL) and programmed death ligand 1 (PD-L1) was analysed in blood mDCs by flow cytometry and in nasal tissue biopsies by dual immunostaining. Blood mDCs were cocultured with (allogeneic) CD4(+) T cells before immunoassays for cytokine responses. RESULTS: mDCs from AR patients expressed a lower level of ICOSL, in both blood and nasal tissue. mDCs from AR were constitutively primed to induce Th2 cytokines and TNF in allogeneic CD4(+) T cells, while no difference was observed for IFN-γ or IL-10. Production of IL-10 and IL-12 did not differ between AR and control mDCs. Blockade of ICOSL in control DCs up-regulated IL-13 but not IFN-γ in cocultures with T cells, while PD-L1 blockade up-regulated both IL-13 and IFN-γ. CONCLUSIONS: Our data show that mDCs from patients with AR display impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant IL-13- and IL-5-producing Th2 cell responses.

Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis.

BACKGROUND: Myeloid (m) and plasmacytoid (p) dendritic cells (DCs) regulate immune responses to allergens, whereas it remains unclear whether abnormal DC function characterizes patients with airway allergy and whether putative dysfunction exists only in target organs. To evaluate DC function from patients with allergic rhinitis (AR), we assessed nasal, cutaneous as well as blood DCs after in vivo and in vitro allergen challenge, respectively. METHODS: DCs were immunostained in nasal and skin tissues, and cytokine expression was assessed by dual immunofluorescence. Cytokine production and regulation of cocultured peripheral CD4+ T cells were assayed by ELISA. RESULTS: In AR patients, local allergen challenge resulted in increases in pDC and mDC numbers at 8 h in the nasal mucosa and at 8-48 h in the skin. Defects in IL-10 and IFN-α were observed in both organs from AR. Blood mDCs from AR exhibited reduced IL-10 and IL-12 expression. The capacity of activated pDCs from AR to produce IFN-α and to trigger IL-10 by allogeneic CD4(+) T cells was diminished, whereas mDCs from these patients supported Th2- and Th17-cell differentiation. CONCLUSION: In allergic rhinitis, DCs are altered not only locally but also in the systemic circulation. mDCs and pDCs increased in airway and skin tissues exposed to the allergen and displayed reduced production of IL-10 and 'type 1 signals' (IL-12, IFN-α) both locally and in blood. Functional studies showed that this results in preferential Th2/Th17-cell polarization and impaired generation by blood DCs of IL-10+ T cells, linking systemic DC dysfunction and biased T-cell responses.

Occupational rhinoconjunctivitis and asthma caused by chicory and oral allergy syndrome associated with bet v 1-related protein.

We report the case of a patient working in a factory producing inulin from chicory who developed rhinoconjunctivitis and asthma to the dust of dry chicory roots and oral allergy syndrome to raw fruits and vegetables. Nonspecific bronchial hyperresponsiveness was diagnosed. A provocation test with dry chicory induced acute rhinoconjunctivitis and an immediate asthmatic response with no further clinical symptoms. Skin prick test results were positive to birch pollen and fresh/dry chicory, and negative for inulin. Specific immunoglobulin (Ig) E was > 100 kU(A)/L for rBet v 1. Specific IgE were detected by immunoblotting chicory extract with the patient's serum, but not with a control serum. The main immunoreactive band corresponded to a protein with a molecular weight of approximately 17 kDa, like Bet v 1, and this immunoreactivity was effectively inhibited by preincubating serum with purified Bet v 1. This case documents occupational rhinoconjunctivitis and asthma due to IgE sensitization to inhaled chicory allergens, including one identified for the first time as a 17-kD Bet v 1 homologous protein, with secondary oral allergy syndrome to related foods.

The effect of colic on oxygen extraction in horses.

Blood oxygen transport and oxygen extraction were assessed in horses with colic. A gravity score (GS) ranging from 1 to 3 was attributed to each colic case with healthy horses used as controls. Jugular venous and carotid arterial blood samples were collected and concentrations of 2,3-diphosphoglycerate, adenosine triphosphate, inorganic phosphate and chloride were determined. pH and partial pressures of carbon dioxide (PCO(2)), and oxygen (PO(2)) were also measured. Oxygen equilibrium curves (OEC) were constructed under standard conditions and oxygen extraction ratios calculated. Haemoglobin oxygen affinity measured under standard conditions (P50(std)) was unchanged in colic horses compared with healthy controls. Horses with the highest GS, i.e. 3 had lower blood pH values than healthy animals. Arterial and venous partial pressures of oxygen at 50% haemoglobin saturation (P50(a) and P50(v)) were significantly higher in horses suffering from colic (GS=3) than in healthy horses. The oxygen extraction ratio was also significantly increased in colic horses with a GS of 3. A rise in the oxygen extraction ratio detected in the most severely affected animals seemed to reflect the compensatory properties of the oxygen transport system where extraction of oxygen from the blood increases when systemic oxygen delivery decreases, as might be anticipated in horses with colic.

Effects of intravenous infusions of sodium bicarbonate on blood oxygen binding in calves with diarrhoea.

Twelve diarrhoeic calves were treated intravenously with an isotonic solution containing sodium bicarbonate, and their oxygen equilibrium curves (OECS) were calculated under standard conditions and compared with those of a group of healthy calves. The relationships between the OECS for arterial and venous blood and the oxygen extraction ratio were investigated. In the diarrhoeic calves, the affinity of haemoglobin for oxygen, measured under standard conditions, was increased compared with the healthy animals. During the infusion, the standard partial oxygen pressure at 50 per cent saturation of haemoglobin (P50) values stayed below the values recorded in the healthy animals. At the end of the infusion the mean standard P50 of the diarrhoeic calves was lower than before the infusion. The combined effects of all the regulating factors on blood oxygen binding resulted in the OECS of the arterial and jugular venous blood of the diarrhoeic calves remaining unchanged compared with the healthy calves. However, the administration of the infusion decreased the P50 of both the arterial and venous blood to below the value recorded in the healthy calves. Oxygen extraction by the tissues was impaired in the diarrhoeic calves throughout the infusion, and they remained dehydrated and depressed until 120 minutes after the infusion began.

Blood-oxygen binding in healthy Standardbred horses.

The purpose of this study was to determine the effect of regulating factors on the oxygen equilibrium curve (OEC) under standard conditions and then to calculate the oxygen extraction between arterial and jugular venous blood in healthy Standardbred horses. The results were compared to those previously obtained in humans and cattle, using the same experimental method. The partial oxygen pressure at 50% saturation of haemoglobin, measured under standard conditions (standard P50), was 24.8+/-2.0 (SD of mean) mmHg. This value was similar to the cattle standard P50 (25.0+/-1.4 mmHg, SD of mean) but lower than the human standard P50 (26.6+/-1.2 mmHg, SD of mean) previously reported using the same experimental method. The effects of regulating factors on the standard OEC were also determined, and a major effect of pH and temperature was noted. In contrast, partial carbon dioxide pressure played only a minor role in horses, compared to cattle and humans. No significant correlation was found between phosphate and chloride concentrations and standard P50.

Haemoglobin oxygen affinity and regulating factors of the blood oxygen transport in canine and feline blood.

Complete dynamic oxygen equilibrium curves (OEC) on dogs and cats whole blood were measured at 33, 37 and 41 degrees C. OEC were also run at three partial carbon dioxide pressures (20, 40 and 80 mmHg) as well as at five pH levels (7.2, 7.3, 7.4, 7.5 and 7.6). 2,3- diphosphoglycerate (DPG) concentrations were determined. Results were compared to those previously published in humans, using the same experimental method [Comp. Biochem. Physiol. 106 (1993) 687]. In standard conditions (pH 7.4, pCO2 40 mmHg and temperature 37 degrees C), the partial oxygen pressure at half-saturation of haemoglobin (p50) was 30.0+/-1.3 mmHg for dogs and 34.1+/-1.8 mmHg for cats. Cat's OEC was thus rightshifted compared to dog's OEC, itself rightshifted compared to human OEC. 2,3-DPG concentrations were higher in dogs than in men until they were very low in cats. Contrary to that observed in human medicine, no significant correlation was identified between standard p50 and canine 2,3-DPG values. Influence of pH, pCO2 and temperature on the OEC was saturation dependent. In dogs, Delta log p50/Delta pH was equal to -0.370, Delta log p50/Delta log pCO2 was 0.093 and Delta log p50/Delta T was 0.020. In cats, Delta log p50/Delta pH was equal to -0.405, Delta log p50/Delta log pCO2 was 0.080 and Delta log p50/Delta T was 0.016. Practically, temperature and pH variations exert a lesser influence in domestic carnivores than in humans, effect of pCO2 being similar in both.

Investigation of the susceptibility of human cell lines to bovine herpesvirus 4 infection: demonstration that human cells can support a nonpermissive persistent infection which protects them against tumor necrosis factor alpha-induced apoptosis.

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we performed in vitro experiments to assess the risk and the consequences of human infection by BoHV-4. First, by using a recombinant BoHV-4 strain expressing enhanced green fluorescent protein under the control of the human cytomegalovirus immediate-early gene promoter, we tested 21 human cell lines for their sensitivity and their permissiveness to BoHV-4 infection. These experiments revealed that human cell lines from lymphoid and myeloid origins were resistant to infection, whereas epithelial cells, carcinoma cells, or adenocarcinoma cells isolated from various organs were sensitive but poorly permissive to BoHV-4 infection. Second, by using the HeLa cell line as a model of human cells sensitive but not permissive to BoHV-4 infection, we investigated the resistance of infected cells to apoptosis and the persistence of the infection through cellular divisions. The results obtained can be summarized as follows. (i) BoHV-4 nonpermissive infection of HeLa cells protects them against tumor necrosis factor alpha-induced apoptosis. (ii) BoHV-4 infection of HeLa cells persists in cell culture; however, the percentage of infected cells decreases with time due to erratic transmission of the viral genome through cell division. (iii) BoHV-4 infection has no effect on the rate of HeLa cell division. Altogether, these data suggest that BoHV-4 could infect humans. This study also stresses the importance of considering the insidious effects of nonpermissive infection when the biosafety of animal gammaherpesviruses for humans is being considered.

Calculation of bovine haemoglobin oxygen saturation by algorithms integrating age, haemoglobin content, blood pH, partial pressures of oxygen and carbon dioxide in the blood, and temperature.

In human and veterinary medicine, arterial and venous haemoglobin oxygen saturations are often used to estimate the severity of a disease and to guide therapeutic decisions. In veterinary medicine, haemoglobin oxygen saturation (SO(2)) is usually calculated using a blood gas analyser and algorithms developed for humans. It is possible, therefore, that the values obtained in animals may be distorted, particularly in animals with a high haemoglobin oxygen affinity, like young calves. In order to verify this hypothesis, we compared the arterial (SaO(2)) and venous (SvO(2)) haemoglobin oxygen saturations calculated using three different algorithms, and the oxygen exchange fraction (OEF) at the tissue level, which is the degree of haemoglobin desaturation between arterial and venous blood (SaO(2)-SvO(2)), with the values obtained from the whole bovine oxygen equilibrium curve (OEC) determined by a reference method. The blood gas analysers underestimated SvO(2) values; consequently, the OEF was overestimated (by about 10%). Two methods of reducing these errors were assessed. As the haemoglobin oxygen affinity decreases during the first month of life in calves a relationship between PO(2) at 50% haemoglobin saturation (P50) and age was established in order to correct the calculated values of venous and arterial SO(2), taking into account the estimated position of the OEC. This method markedly reduced the error for SvO(2) and OEF. Secondly, the SO(2) was calculated using a mathematical model taking into account the age of the animal and the specific effects of pH, PCO(2), and temperature on the bovine OEC. Using this method, the mean difference between the OEF values calculated using the mathematical model and those calculated by the reference method was close to zero. The errors produced by blood gas analysers can thus be minimised in two ways: firstly, by simply introducing a P50 estimated from the age of the calf into the analyser before the measurement; and secondly, by calculating the SO(2) using a mathematical model applied to the bovine OEC.

Blood oxygen binding in calves with naturally occurring diarrhea.

OBJECTIVE: To assess blood oxygen binding in calves with diarrhea. ANIMALS: 22 dairy and 26 double-muscled calves with diarrhea, 31 healthy dairy calves and 37 healthy double-muscled calves. PROCEDURE: Severity of disease, including the ability of affected calves to stand, was evaluated. Hydration and signs of depression were scored. Venous and arterial blood samples were collected, and 2,3-diphosphoglycerate, ATP, chloride, inorganic phosphate, lactate, pyruvate, total protein, albumin, and hemoglobin concentrations, and Hct, pH, Pco2, and PO2 were determined. Oxygen equilibrium curves (OEC) were constructed under standard conditions, and oxygen extraction ratios were calculated. RESULTS: Recumbent calves of both breed-types were more dehydrated and had more severe signs of depression than ambulatory affected calves. In both breed-types, hemoglobin oxygen affinity was increased in calves with diarrhea, compared with healthy calves, as indicated by a decrease in standard partial oxygen pressure (P50). Diarrhea induced hypocapnia and hypothermia in the most severely affected calves, which counteracted the acidosis-induced right shift in arterial and venous OEC. Arterial and venous P50 were significantly less in double-muscled calves with diarrhea than healthy calves, whereas P50 for affected dairy calves were similar to those of healthy calves. Except in the most severely affected dairy calves, oxygen extraction ratio was significantly less in calves with diarrhea, compared with healthy calves. CONCLUSIONS AND CLINICAL RELEVANCE: Release of oxygen from blood may be impaired in calves with diarrhea, depending on the effect of the disease on certain blood biochemical variables.

Blood oxygen binding in double-muscled calves and dairy calves with conventional muscle conformation.

OBJECTIVE: To assess in vivo blood oxygen binding in double-muscled calves and dairy calves with conventional muscle conformation. ANIMALS: 58 dairy and 48 double-muscled calves. PROCEDURE: Calves were classified as neonatal (24 hours old) or older calves (2 to 26 days old). Venous and arterial blood samples were collected, and hemoglobin concentration, pH, PCO2, and PO2 were determined. Blood oxygen equilibrium curves (OEC) under standard conditions were constructed, and the oxygen exchange fraction (OEF) and the amount of oxygen released at the tissue level by 100 ml of blood (OEF Vol%) were calculated. RESULTS: In each breed, partial pressure of oxygen at 50% saturation of hemoglobin (P50) under standard conditions was significantly higher in older than in neonatal calves, indicating a right shift in OEC with age. Venous P50 was significantly lower in neonatal double-muscled calves than in neonatal dairy calves, but arterial and venous P50 were significantly higher in older double-muscled calves than in older dairy calves. In double-muscled, but not in dairy, calves, OEF was significantly higher in older than in neonatal calves. In neonatal calves, OEF Vol% was not significantly different between breeds, but OEF Vol% was significantly higher in older double-muscled calves than in older dairy calves. CONCLUSIONS AND CLINICAL RELEVANCE: The lower OEF in neonatal double-muscled calves, compared with dairy calves, could contribute to the higher sensitivity of double-muscled calves to hypoxia. Blood oxygen affinity decreased with age, but OEF and OEF Vol% were unchanged with age in dairy calves, whereas they increased with age in double-muscled calves.

Effect of inorganic ions on the oxyhemoglobin dissociation curve of severely ill patients.

We have shown that administration of inorganic potassium phosphates (Pi) to patients with severe diabetic ketoacidosis was able to increase the P50 (the PO2 necessary to achieve a hemoglobin saturation of 50%) by a non diphosphoglycerate (DPG) mediated effect. This suggests that the oxyhemoglobin dissociation curve (ODC) may be determined not only by pH, temperature, CO2 content and DPG but also by plasmatic ions. In order to test this hypothesis we have determined the ODC on whole blood in two groups of subjects, 49 control subjects with matching age and sex and 49 patients suffering from liver cirrhosis, acute pancreatitis, septic shock and acute respiratory distress syndrome. The patients had many ionic disorders induced either by their diseases or by the applied treatment. The mean ODC of the patients did not differ from the normal values. In contrast, the dispersion of PO2 around the saturations values was increased from 5 to 80% saturation. A forward regression analysis showed that the DPG level and the levels of inorganic phosphates and natrium (Na+) played a significant role in determining the position of the ODC according to the following equation: P50 (mmHg) = 34.5 + 0.225 DPG + 0.62 Pi-0.09 Na+, where DPG is in micromol.gHb-1 and Pi and Na+ in mEq.l-1. In separate experiments we showed that the Bohr effect as expressed in d (log PO2)/dpH amounted to -0.53, -0.46 and -0.42 for SO2 equal to 5%, 50% and 95%, respectively. The corresponding values for the temperature effect was expressed in d (log PO2)/dT amounted to 0.028, 0.024, and 0.020 respectively. The fact that ions play an role in regulating the position of the ODC of patients with ionic disorders may have therapeutical implications, preventive or curative.

Effects of hyperchloremia on blood oxygen binding in healthy calves.

Three different levels of hyperchloremia were induced in healthy Friesian calves to study the effects of chloride on blood oxygen transport. By infusion, the calves received either 5 ml/kg of 0.9% NaCl (low-level hyperchloremia; group A), 5 ml/kg of 7.5% NaCl (moderate hyperchloremia; group B), or 7.5 ml/kg of 7.5% NaCl (high-level hyperchloremia; group C). Blood was sampled from the jugular vein and the brachial artery. Chloride concentration, hemoglobin content, arterial and venous pH, PCO2, and PO2 were determined. At each time point (0, 15, 30, 60, and 120 min), the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions. In groups B and C, hyperchloremia was accompanied by a sustained rightward shift of the OEC, as indicated by the significant increase in the standard PO2 at 50% hemoglobin saturation. Infusion of hypertonic saline also induced relative acidosis. The arterial and venous OEC were calculated, with body temperature, pH, and PCO2 values in arterial and venous blood taken into account. The degree of blood desaturation between the arterial and the venous compartments [O2 exchange fraction (OEF%)] and the amount of oxygen released at tissue level by 100 ml of bovine blood (OEF vol%) were calculated from the arterial and venous OEC combined with the PO2 and hemoglobin concentration. The chloride-induced rightward shift of the OEC was reinforced by the relative acidosis, but the altered PO2 values combined with the lower hemoglobin concentration explained the absence of any significant difference in OEF (% and vol%). We conclude that infusion of hypertonic saline induces hyperchloremia and acidemia, which can explain the OEC rightward shift observed in arterial and peripheral venous blood.

Assessment of the lactate biosensor methodology.

The rapid determination of lactate level is useful for clinical emergencies, as in the case of shock conditions or during surgical operations, as well as in numerous cases of respiratory failure, in cardiac or paediatric pathology and during exercise tests. Moreover, it is of prognostic significance in critically ill patients. Photometric methods are slow and, even when performed in good conditions, will give results only 30 min after blood collection, during which time the clinical condition of the patient may change. In this study, we have assessed the lactate biosensor, a method that yields lactate measurements in less than 1 min with only 100 microL of biological fluid. In order to test the validity of this method, we performed comparisons between the Sigma classical enzymatic reference method and two commercially available biosensors: the Ciba-Corning biosensor 865 and the Yellow Springs lactate biosensor. Lactate measurements were performed in heparinized arterial blood samples without antiglycolitic agent (n=71). In order to cover a wide range of lactate levels, samples came from patients admitted to the intensive care unit for severe conditions and patients addressed for bicycle exercise testing. Each whole blood sample was processed in duplicate by both biosensors. For plasma measurement, subsamples of whole blood were centrifuged and the resulting plasma were processed by the biosensors and the Sigma method. Two parameters that can potentially influence lactate measurement were also investigated: haematocrit and total protein levels. The data showed that measurements performed on plasma are satisfactory for both biosensors. For whole blood, the Ciba-Corning device gives accurate results but the Yellow Springs apparatus seriously underestimates lactate levels. This underestimation is strongly influenced by the haematocrit level, so that a correction factor can be calculated (based on the haemoglobin level), which allows accurate "corrected" results to be obtained for whole blood with the Yellow Springs analyser.

Right shift of the oxyhemoglobin dissociation curve in acute respiratory distress syndrome.

Deep hypoxia is known to increase the intraerythrocytic 2,3 diphosphoglycerate (DPG) level and therefore to induce a right shift of the oxyhemoglobin dissociation curve (ODC), which is considered to be a protective mechanism against tissular hypoxia. Our purpose was to assess whether the ODC is shifted to the right in patients with acute respiratory distress syndrome (ARDS) and whether this shift had a beneficial effect on tissue oxygenation. We have determined the whole ODC and related indices in 29 control subjects and 29 patients suffering from ARDS for at least 5 days. The ODC of the patients were shifted to the right from 20 to 95% saturation. Their DPG level was increased (19.9 +/- 3.9 mumol/gHb, mean +/- SD) as compared to control subjects (12.5 +/- 2.1 mumol/gHb). There was a highly significant relation in patients between their P50 (pO2 necessary to achieve 50% saturation) and their DPG according to the equation: P50 (kPa) = 0.03 DPG (mumol/gHb) + 3.24 (r = 0,54) (p < 0,001). It is likely that in such patients hypoxia is severe enough to stimulate the DPG synthesis and induce a right shift of the ODC. It is not at all certain that this shift has a favourable effect on tissue oxygenation. Indeed, the extreme values for PaO2 were from 3.43 to 7.96 kPa that correspond to SO2 of 48 to 91% where the ODC has not yet his upper part. A right shift decreases therefore the captation of oxygen from the lung. On the other hand theoretical studies have shown that at low arterial PO2 values a right shift of the ODC has a detrimental effect on release of oxygen from hemoglobin if the mixed venous PO2 is decreased. In order to quantify the amount of oxygen actually transmitted to the tissues, others factors are to be investigate as the PCO2 or the temperature.

Influence of age and breed on the binding of oxygen to red blood cells of bovine calves.

The influence of somatic growth and genetic selection on the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions in double-muscled and dairy calves during their first 3 mo of life. Crossbreed animals were also investigated. Hemoglobin, 2,3-diphosphoglycerate (DPG), Cl, and Pi concentrations were also measured. The percentage of fetal hemoglobin (HbF) was determined. The influence of exogenous Cl, Pi, and pH on the OEC was also assessed. The PO2 at 50% hemoglobin saturation (P50) increased during somatic growth, probably because of the increase in DPG recorded in double-muscled neonates and to the progressive disappearance of HbF in both breeds. The oxygen exchange fraction (OEF%) was used to assess the combined influence of the OEC shift and OEC shape changes on blood oxygen desaturation under standard conditions, when the PO2 decreases within a physiological range. The OEF% showed an increase during the first month, then a stabilization. The effects of Cl, Pi, and pH in Friesian calves were similar as in adult cattle. Double-muscled neonates had a lower P50, OEF% values, and DPG concentrations and higher hemoglobin and Cl concentrations than Friesian neonates. The Pi concentration and the percentage of HbF were similar in both breeds. The pH and the Cl concentration had significantly less effect on the OEC in double-muscled than in Friesian calves. Crossbreed animals exhibited intermediate parameter values, between those recorded for double-muscled and Friesian calves. All differences between breeds progressively disappeared during the first month. These data show that blood function changes markedly in calves during the first month of life and that genetic selection can alter blood function.

Plasmatic ions influence the oxyhemoglobin dissociation curve of patients with chronic obstructive lung disease.

Chronic hypoxemia, carboxyhemoglobin and ionic disorders as induced by drug intake may a priori influence the oxyhemoglobin dissociation curve (ODC) of patients suffering from chronic obstructive lung disease (COLD). We have traced the ODC and related indices on whole blood of 54 normal non smoking subjects and of 54 ambulatory smokers or ex-smokers COLD patients whose the FEV1 was 1.17 +/- 0.45 litres (mean and SD) and the resting PaO2 63.3 +/- 7.7 Torr. In COLD patients HbCO induces a left shift of the ODC according to the following equation: P50 (Torr) = 27.6-0.4 (HbCO-1) where P50 is the PO2 necessary to saturate hemoglobin at 50%. When normalized for HbCO level of 1% there was no difference in the ODC of the two groups. In contrast, the dispersion around the mean was significantly more important in patients than in control subjects from 20 to 90% SO2. We attributed this fact to ionic disorders that were present in 51 out of the 54 patients and were presumably due to drug intake. The P50 (Torr) = -35.55 + 0.325 (Na+) + 0.096(Cl-) + 0.27 (total CO2), r = 0.73, where Na+, Cl- and total CO2 were expressed in mEq/l. We concluded that: 1) hypoxemia was not deep enough in our patients to shift their ODC to the right; 2) plasmatic ions influenced their ODC; 3) and when possible, it is important to correct ionic disorders either by a curative or a preventive approach.

Chloride and inorganic phosphate modulate binding of oxygen to bovine red blood cells.

The influence of Pi and Cl on the equilibrium of oxygen binding to bovine red blood cells was assessed by plotting the whole blood oxygen dissociation curve measured under standard conditions with and without added KCl and K2HPO4. Both salts shifted the oxygen dissociation curve to the right. This effect was more marked at the highest saturation levels. At a given saturation level, the anion-induced shift was linearly related to the concentration of salt added to the blood. Cl had a greater effect than Pi. The relationship between changes in Po2 at 50% hemoglobin saturation (in Torr) and concentrations of ions added (in mmol/l) was equal to 0.0515[Cl] + 0.0302[Pi] (r2 = 0.94; P < 0.001). These changes were not due to the hyperosmolality induced by salt addition, since sucrose added in place of salts was without effect on the measured parameters. The oxygen exchange fraction expressed as percentage of saturation, i.e., the difference in hemoglobin saturation when Po2 decreases from 130 to 40 Torr, was linearly correlated to added anion concentration (in mmol/l) (= 0.102[Cl] + 0.059[Pi] (r2 = 0.95; P < 0.001)). No significant interaction between the anions was observed; their effects were purely additive. This original mechanism of controlling the oxygen affinity of bovine blood may have clinical relevance: Cl and Pi could be used to increase oxygen transport efficiency in hypoxic animals.