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Introduction: The oxyhemoglobin dissociation curve describes the relationship between the partial pressure of oxygen and the percent of hemoglobin saturated with oxygen. This relationship is a sigmoidal shaped curve. The oxyhemoglobin dissociation curve varies from patient to patient. If patient variability could be determined patient specific oxygen flow rates could be delivered. We have developed a model for characterizing patient specific variations in SpO2. Our model predicts saturation by generating a patient-specific oxyhemoglobin dissociation curve. The purpose of this study was to determine the effectiveness of our patient-specific model. Methods: We Probed SpO2 level at various oxygen inhalation amounts to provide input to our model. We linearized the relationship between SpO2 and EtO2 for each participant. We then fit a line to those linearized data points. We used model fit error techniques to show the ability of the model to fit volunteer and patient SpO2. Fit results were generated by using the fitted patient specific curve shift to estimate oxygen concentrations. Fit errors were used to assess the model’s ability to fit SpO2 and to make an accurate patient specific oxyhemoglobin dissociation curve. Results: Thirty subjects participated in our volunteer study. The nominal average line is quite close to the standard curve. The cumulative density plot of the model fit error for the entire data set in our volunteer study and the average for each volunteer had greater accuracy than the standard fit. Sixty patients participated in our clinical trial. The nominal average line is quite different than the standard curve. The cumulative density plot of the model fit error for the entire data set in our clinical study and the average for each patient both had greater accuracy than the standard fit. Discussion: This study has shown that our model is able to fit patient saturation values with higher accuracy compared to using the standard oxyhemoglobin dissociation curve. We have also shown that the variability of the ODC from patient to patient is quite large, making predicting patient saturation quite difficult. We have developed and tested a model for fitting the oxyhemoglobin dissociation curve to patients. We have shown improved fit when compared to the standard oxyhemoglobin dissociation curve. This model could potentially be used to predict time to desaturation specific to a patient.

Shyang-Yun Pamela K. Shiao, PhD, FAAN, RN Purpose: To examine the accuracy of oxygen saturation (SO2 )i nr elation to blood oxyhemoglobin (HbO2) measurements with the effects of fetal hemoglobin (HbF) determined and their oxyhemoglobin dissociation curves. Method: Twenty neonates with gestational ages ranging from 25 to 34 weeks, who had umbilical arterial or venous lines inserted, were investigated. Analyses were performed with 169 arterial and 41 venous blood samples from these infants by employing HbF- and HbA-mode (as controls) blood analyses, using a hemoximeter. Results: Without adjusting the effects of HbF when using HbA-mode analyses, mean SO2 measurements were elevated for 5% (±1.38) compared with the results of HbF-mode analyses, with 3.5% elevated HbCO levels for the total blood samples. With left-shifted oxyhemoglobin dissociation curves in neonates, for the critical values of oxygen tension values between 50 and 75 mm Hg, arterial HbO2 ranged from 94% to 96%, SaO2 from 97% to 98%, and SpO2 from 96% to 97% (compared to 85%–94% in healthy adults). Conclusions: The left-shifted oxyhemoglobin curves warrant the importance of accurate measurements of oxygenation status for neonates. Fetel hemoglobin determination is essential for accurate SO2 measurements and the assessment of proper oxygenation status in neonates. Key words: fetal hemoglobin, oxygen saturation

Introduction: The amount of oxygen in blood is an important measure of lung function. There are three ways to quantify the amount of oxygen in blood: 1) the oxygen tension (PO2); 2) the percent of hemoglobin saturated with oxygen (HbO2); and 3) the absolute content of oxygen in the blood (ContO2). PO2 is commonly measured. HbO2 and ContO2 are usually calculated from the normal human oxyhemoglobin relationship, but can be measured directly. The canine curve is similar to, but not the same as, that of humans. The purpose of this study was to compare, in dogs, direct measurements of HbO2 and ContO2 with analyzer-calculated values derived using the human oxyhemoglobin curve, and with hand-calculated values derived using a canine oxyhemoglobin curve. Materials And Methods: Arterial and jugular venous samples from 17 healthy dogs were analyzed by an ABL 705 blood gas and electrolyte analyzer, an OSM3 co-oximeter, and a LexO2con oxygen content analyzer. HbO2 was calculated from the measured PO2 using a published formula based on normal canine data (Reeves, 1982), and compared to measured and analyzer-calculated values. ContO2 values were calculated, and compared to measured and analyzer-calculated values. Means and standard deviations were compared by analysis of variance for repeated measures. Differences were considered significant at p

Background: This study compares oxyhemoglobin dissociation during the nonperfused periods of hypothermic cardioplegic arrest in two blood cardioplegic solutions with different hemoglobin concentrations. The hypothesis is that more oxygen will dissociate from hemoglobin in a blood cardioplegic solution with a higher hemoglobin content than from a cardioplegic solution with a lower hemoglobin content. However, the increment in the volume of oxygen that dissociates from hemoglobin will be less than anticipated by a ratio of hemoglobin concentrations in the cardioplegic solution. Methods and results: Pigs ( n = 22) were supported by bypass and subjected to 60 minutes of hypothermic cardioplegic arrest with either a high-hemoglobin ( n = 10) or low-hemoglobin ( n = 12) blood cardioplegic solution. Aortic root and coronary sinus blood samples were obtained before bypass and 5 seconds after the start of cardioplegic infusions at 20, 40, and 60 minutes of cardioplegic arrest. Oxyhemoglobin dissociation occurred in both experimental groups during the ischemic intervals of cardioplegic arrest. However, there were no significant differences between the high- and low-hemoglobin groups in the arterial-venous oxygen content differences for samples taken after each of the three ischemic intervals ( p values: control=0.78; cardioplegia interval 1=0.95; interval 2=0.56; and interval 3=0.12). Conclusions: The present study emphasizes the inherent limitations of unmodified erythrocyte hemoglobin as an oxygen source in hypothermic alkalotic cardioplegic solutions. These limitations may be obviated by methods that increase the dissolved oxygen content of the cardioplegic solution or methods that decrease the affinity of hemoglobin for oxygen under conditions of hypothermia and alkalosis. (J THORAC CARDIOVASC SURG 1994;108:664-71)

A detailed computational model is developed to simulate oxygen transport from a three-dimensional (3D) microvascular network to the surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O2 consumption, myoglobin-facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O2 transport and is capable of incorporating realistic 3D microvascular network geometries. Simulations in this study were performed using a computer-generated microvascular architecture that mimics morphometric parameters for the hamster cheek pouch retractor muscle. Theoretical results are presented next to corresponding experimental data. Phosphorescence quenching microscopy provided PO2 measurements at the arteriolar and venular ends of capillaries in the hamster retractor muscle before and after isovolemic hemodilution with three different hemodilutents: a non-oxygen-carrying plasma expander and two hemoglobin solutions with different oxygen affinities. Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O2 is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O2 transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood substitutes.

Have you ever asked one of your nursing colleagues for an explanation regarding the rationale for performing a procedure or administering a medication in a specific way and heard the response, “that is just the way we do it”? Have you been informed by one of the senior nursing staff, “because that is how the doctor has ordered it”? Having heard those answers multiple times during my nursing career, I now like to designate those types of query responses as “nursing myths.” A myth is defined as “an ill-founded belief held uncritically by an interested group” in Webster’s dictionary.1 In other words, a myth is using an approach in the delivery of patient care that is unsupported by evidence-based practice. In a previous column published in the Journal of Vascular Nursing, it was noted that evidence-based practice uses external confirmation as the guide for deciding whether to support nursing decisions in delivering individualized patient care.2 Although research is typically the method used to validate a particular nursing practice, it is not the only way. As a Critical Care Clinical Nurse Specialist developing practice guidelines for my institution, I have attempted to use research findings as the springboard from which to derive educational materials, protocols, and algorithms. The use of research findings provides a basis for critical thinking—not uncritical thinking and not myths. Delving into these various studies during the development of the protocols increased my interest in the research process and led me to begin the pursuit of a doctorate in nursing. One of the nursing guidelines being developed involved the postoperative care of the patient after lower extremity peripheral artery revascularization. Recent statistics indicate that in 1996, approximately 95,000 lower extremity peripheral arterial revascularization procedures were performed in the United States to restore circulation to the ischemic limb.3 After surgery, the maintenance of blood flow and tissue oxygenation to the revascularized limb was a nursing responsibility. Furthermore, extremity positioning was the usual method to promote optimal circulation. My question was, what is considered the best position in which to place the revascularized extremity? While writing the nursing guidelines for my institution, I found different recommendations in various nursing references. Smeltzer and Bare,4 Lewis,5 and Gulanick et al6 advocated extremity elevation as a standard. Fahey and McCarthy7 and Herbert8 recommended limb elevation when postoperative edema is present. Urban et al9 and Maxwell-Thompson and Yuan10 did not address the postoperative peripheral vascular surgery limb position. These differing recommendations, or lack of recommendation, led to further questions. Was there an optimal limb position that would maintain tissue perfusion in the revascularized extremity? Were these examples of nursing myths? Was there research that measured the lower extremity response to position changes after arterial revascularization surgery? These studies would provide the quantitative data or evidence to support the nursing practice. A literature search was initiated in an attempt to resolve these questions. I have been enamored with technology and its ability to help incorporate findings in a plan of care since my first staff nurse position in a combined intensive care unit/coronary care unit/cardiovascular unit. Consequently, my focus became twofold. The first purpose was to uncover studies that provided an answer to the question of optimal limb position after peripheral vascular surgery. The second purpose was to identify a physiologic instrument used during these analyses that easily and noninvasively measured the revascularized lower extremity tissue perfusion. Through these findings, I hoped to clarify the research questions that could answer this issue and that would be further pursued during my doctoral nursing work. Results of the literature review revealed several items. First, there was a paucity of research regarding extremity positioning in the patient after peripheral arterial vascular surgery. Second, a number of these studies used the technique of transcutaneous oxygen measurements (also known as TcPO2 or TCOMs) to noninvasively ascertain the underlying tissue perfusion. This method uses a heated electrode that is placed on the skin. Simplistically, the epidermal warming “arterializes” the underlying dermal capillary blood flow through arteriolar vasodilation, decreased dermal capillary resistance, improved diffusion, and a shift in the oxyhemoglobin dissociation curve.11,12 Reliability and validity of the TcPO2 measurements had been established by multiple researchers.13-15 If a patient had lower extremity periphKathleen Rich, MS, RN, CCNS, is a Critical Care Clinical Specialist for the Methodist Hospitals, Inc, Gary, Indiana.

Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of particular importance in SCD. To assess the accuracy of pulse oximetry in the diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of arterial oxygen saturation (SpO2) in adult patients with SCD and acute vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 = oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co-oximetry. We accepted SpO2 readings only if they were stable and characterized by strong and regular photoplethysmographic waves on the oximeter screen. To assess the position of these patients' oxyhemoglobin dissociation curves, we plotted arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin percentage (by an average of 3.4 percentage points), but it almost always accurately estimated SaO2 (underestimating on average by 1.1 percentage points). The error in SpO2 was never enough to classify a hypoxemic patient erroneously as normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as strong and regular photoplethysmographic waves are present, pulse oximeters can be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.

A new approach to the development of an oxygen-carrying blood substitute is presented. The development of a viable blood substitute in the form of a multiple emulsion encapsulating hemoglobin solution was explored. Results indicated that the formulation ingredients and procedure affect the properties of the multiple emulsion. In order to evaluate the different formulations a quantitative method of assessing the encapsulation efficiency (yield) of the multiple emulsions was developed. The yield test measures the amount of hemoglobin released into the external phase. A model mutiple emulsion was formulated and characterized by yield, drop size distribution, oxygen-carrying capacity, oxyhemoglobin dissociation, short-term storage stability, and viscosity. The yield obtained for the model formulation was excellent (greater than 90%) giving high oxygen-carrying capacity. The high yield was maintained over a four day storage period at 4dC.

Blood from non-smoking donors was incubated with Althesin and the PO2 for half-saturation of haemoglobin at standard pH, PCO2 and temperature (P 50) was measured. The mean P 50 values of blood with blood concentrations of Althesin of 0.14 ml/dl and 0.42 ml/dl were greater (1.14 +/- 0.31 (SEM) mm Hg (P less than 0.005) and 2.22 +/- 0.35 (SEM) mm Hg (P less than 0.001), respectively) than that of control blood. These increases were dose-dependent (P less than 0.05). Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentrations were not significantly different between the Althesin-treated and the control blood. Although a decrease in the affinity of haemoglobin for oxygen in vitro in the presence of Althesin was statistically significant, this would have no clinical significance if the drug was being used for the induction of anaesthesia only.

The Travenol Hem-O-Scan and the Instrumentation Laboratory (IL) system for determination of the oxygen dissociation curve and P50 values have been evaluated. Using the Hem-O-Scan, an oxygen dissociation curve and P50 value may be obtained on 2 microliter of blood in 40 min, though the pH is not measured. In the IL system, approximately 3 ml of blood is required to establish four points on the oxygen dissociation curve in 80 min, and pH data are available. Both systems give reproducible results for P50, giving standard deviations of 0.786 mm Hg for the Hem-O-Scan and 0.949 mm Hg for the IL system, compared with 1.740 mm Hg for the manual system. Good agreement was found between the manual method and Hem-O-Scan (t = 0.363, degrees of freedom = 19, 0.8 greater than P greater than 0.7; r = 0.892, P less than 0.001). There was also satisfactory agreement between the IL system and the Hem-O-Scan (t = 0.370, degrees of freedom = 20, 0.8 greater than P greater than 0.7; r = 0.760, P less than 0.001). P50 values obtained by the manual and by both automated technics agree well with published values.

Computer simulation studies have been carried out to ascertain whether the mixing technique for the determination of oxyhemoglobin dissociation curves, combined with nonlinear least-squares optimization, can supply accurate values for the equilibrium constants of Adair's equation. The results show that reasonable estimates of those constants can in principle be obtained, the accuracy being greatest for the constants that govern the upper saturation range of the binding curve. There is, however, no successful method for establishing confidence intervals on the parameters obtained from individual experiments. Finally, some published oxygen dissociation curves have been reanalyzed, and some recently reported values for the Adair constants of whole blood are shown to be incorrect.

The mathematical analysis of steady state oxygen distribution in a Krogh cylinder is presented in this paper. Perturbation techniques are used to determine the effect of axial diffusion when the diameter of the Krogh cylinder is small compared to its length. Separate asymptotic expansions are developed for the arterial end, the central region, and the venous end of the Krogh cylinder. Solutions are obtained for each of these regions, and they are combined, using the methods of matched asymptotic expansions, to obtain a solution that is uniformly valid throughout the entire Krogh cylinder. The accuracy of the perturbation analysis is examined by comparing the approximate solution with the exact solution for the case of a linear oxyhemoglobin dissociation relationship. A simple analytic criterion is derived for determining when axial diffusion is important and when it can be neglected.

The intraerythrocytic level of 2,3-diphosphoglycerate and the oxygen affinity of hemoglobin in the red cell are shown to be strongly dependent on the intraerythrocytic pH. This effect should be taken into account when evaluating the increase in 2,3-diphosphoglycerate found at hypoxemic and anemic hypoxia. It was also demonstrated that high concentrations of inorganic phosphate in serum influence the intraerythrocytic 2,3-diphosphoglycerate concentration.

Summary 1.The in vivo position of oxyhemoglobin dissociation was determined in 8 control subjects and in 9 patients with documented hepatic cirrhosis by the estimation of arterial pH, oxygen pressure, and percentage of saturation of hemoglobin with oxygen. 2.Cirrhotic patients with hepatic encephalopathy demonstrated a significant right shift of the oxyhemoglobin dissociation curve when compared to controls or to cirrhotic patients without encephalopathy.

1.1. Oxyhemoglobin dissociation curves were obtained from in vivo studies of maternal, fetal and neonatal sheep blood. Similar studies using slightly different techniques were performed on human maternal and fetal blood. 2.2. In the sheep, the in vivo analysis results in oxygen dissociation curves that are shifted to the left of those reported by others. The fetal curves lie to the left of maternal with the neonatal in between. In the human, the fetal curve is shifted to the right and is not significantly different from the maternal curve. 3.3. Oxyhemoglobin dissociation characteristics are probably influenced by the use of metabolic antagonists and by the passage of time required for analysis of the blood. These factors may alter the ionic distribution between plasma and erythrocytes and, hence, affect the oxygen affinity of the blood.

The in vivo oxyhemoglobin dissociation curves of patients with liver disease appear to be displaced to the right of those of normal men. Although the displacement is small it may contribute to the arterial unsaturation which sometimes occurs. hemoglobin; oxygen electrode; unsaturation Submitted on March 9, 1964

A magnetic method for the determination of oxyhemoglobin dissociation curves has been employed in a study of the oxygen affinity of hemoglobin in simple solution and in normal and spherical erythrocytes. Hemoglobin within the biconcave discoid cell was shown to have a lower affinity for oxygen than that in the spherical cell. The oxygen affinity of hemoglobin within the spherical cells was the same as hemoglobin in simple solution. The molecular interpretation of the observed equilibrium between oxygen and hemoglobin supports previous evidence that oxygen molecules react in pairs with the hemoglobin molecule.

A method for direct determination of hemoglobin oxygen saturation at predetermined values for pH, PCO2 , PO2, and temperature is described, and its applicability to studies of the oxygen dissociation curve for whole blood under various controlled conditions is discussed and illustrated.

The oxyhemoglobin dissociation curves for goose blood were determined at pH values of 7.25, 7.4 and 7.6. Curves were constructed by polarographic analyses of O 2 tension and spectrophotometric determination of Hb saturation. The curves obtained showed a significant displacement to the right in comparison with human dissociation curves. Also, the hemoglobin saturation never exceeded 95 % up to an oxygen tension of 150 mm Hg (pH 7.40). Bohr effect Oxygen dissociation curve T50

A mathematical model of placental oxygen transfer is used to argue that the experimentally observed control of fetal oxygen concentration in fetal lambs can be explained by the nature of oxyhemoglobin dissociation functions and the differences between these functions in fetal and maternal blood. It is not essential to the explanation to posit any mechanisms responding to a pO2 sensor or any changes in fetal, maternal, or placental vascular structures. Equally unnecessary are assumed alterations in the physical or chemical structure of placental membranes. (Aurthor)

Many investigators have endeavored to accurately measure oxygen content produced or consumed from substrates or tissues. Most of the techniques currently available are time consuming or exceedingly complex. Many require expensive apparatus and demand the skills of a highly trained technician. We have deveoloped a rapid and sensitive method of measuring oxygen content or consumption. This method is based upon the time for polymerization of acrylamide gels. The time of acrylamide polymerization is directly proportional to the oxygen content of the test medium. We have used this method to generate oxyhemoglobin dissociation curves which closely resemble those published by Severinghaus and Duvelleroy, as well as those we determined by the conventional Van Slyke analysis. We have also used this method to measure the oxygen consumption of tumor cells and to evaluate the effects of Actinomycin, cyclohexamide and cytosine arabinoside on Walker 256 ascites tumor. The results correlate with the known in vivo effects of these drugs on this tumor cell line. Therefore, because of its sensitivity and adaptability this method may be useful in a variety of clinical and biological situations.

Shifts in the oxygen dissociation curve (O.D.C.) have been taken into account when studying oxygen delivery to tissue as a dependent factor of oxygen availability. It can be assumed that changes in the oxyhemoglobin dissociation characteristics of the blood will have a certain effect on the amount of oxygen available (1,2).

1. 1. A spectrophotometric method can be used to measure oxyhemoglobin dissociation in opossums at optical densities of 500 and 592 nm. 2. 2. Opossum hemoglobin spectrogram reveals a double-humped curve for oxygenated hemoglobin and a single-humped curve for reduced hemoglobin. 3. 3. The P50 calculated by the above method at pH 7·4, 35°C and 40 mm Hg Pa CO2 is 35·0 mm Hg of oxygen.

Techniques for reducing measured oxyhemoglobin saturation data to standard conditions and determining the coefficients of a mathematical model of the oxyhemoglobin dissociation curve (ODC) have been developed and programmed for a digital computer. Using a device which measures PO2, oxygen content, and pH simultaneously throughout the physiologic range, coefficients of a measured ODC may be produced for any blood sample. Data from a group of blood samples may be pooled to determine the coefficients of an average ODC and to estimate the statistical certainties and ranges about it. Use of these techniques was demonstrated on a group of healthy subjects, patients who had recently received blood transfusions, and patients who had recently suffered myocardial infarction. Substantial shifts of the ODCs to the right and left of the “standard” curve were noted in the myocardial and transfusion patients, respectively, and in the average ODCs of these groups. The standard mean ODC was found to lie within or near to the 95% confidence limits of the mean ODC of the healthy group at all points. It is now possible to measure the continuous affinity of hemoglobin for oxygen in a blood sample drawn from a patient, and to use his individualized ODC in the calculation of saturation from PO2. It is also possible to determine the average ODC for a homogeneous group of blood samples, and thereby to increase the accuracy and specificity of certain clinical computational procedures.

Practically all information available on the range of normal variation in the position and shape of the oxygen dissociation curve is based on multiple point determinations of O2 content or saturation at a specific PO2, constant pH and temperature. Less is known concerning the affinity of hemoglobin for oxygen following different kinds of trauma e.g. skin burns.

The intraerythrocytic 2,3-diphosphoglycerate concentration decreases with decreasing pH below 7.40. Oxyhemoglobin dissociation is thereby changed, the oxygen affinity being increased. This effect counteracts the Bohr-effect, also quantitatively, leading to a nearly constant oxygen affinity at low pH values. The effect of anaerobic incubation on the 2,3-diphosphoglycerate level could be explained in terms of changes in intraerythrocytic pH caused by the deoxygenation of hemoglobin.

Normal hemoglobin function depends on adequate erythrocyte levels of 2,3-diphosphoglycerate (2,3-DPG), a compound that is poorly maintained during blood bank storage in acid-citrate-dextrose (ACD). Since 2,3-DPG is better maintained at the higher pH afforded by citrate-phosphate-dextrose (CPD), hemoglobin function was compared during storage in CPD and ACD. Further, hemoglobin function was studied in CPD blood containing adenine and inosine, compounds that provide metabolic energy and thus prolong the shelf-life of blood, because they also effect the levels of 2,3-DPG during storage. Hemoglobin function, expressed as the P50 (the P02 at 50 per cent oxygenation, an inverse but direct measure of oxygen affinity) is considerably better maintained during storage in CPD than in ACD. The hemoglobin function or P50 of blood stored in CPD-adenine is not maintained as well as blood stored in CPD without adenine, but the oxyhemoglobin dissociation curves show only a small difference when compared to the difference between ACD and CPD. Blood stored in CPD-adenine with inosine, present initially or added at day 25, allows higher P50 values late in storage, thus providing better hemoglobin function for more of the storage period.

1. 1. Oxyhemoglobin dissociation curves of four different species of porpoises and one sea lion species have been made. 2. 2. Porpoises which swim faster and dive longer and deeper have greater hemoglobin oxygen affinity than the slower-swimming, shallower and shorter-diving species. 3. 3. The similarity and relationship of the dissociation curves in these sea mammals to those observed in some terrestrial species living under hypoxic conditions are emphasized. 4. 4. Electrophoretic patterns of the hemoglobins are shown.

A study of P50 (pO2 at 50% saturation, 37 C., pH 7.4) values determined by classic tonometry methods on blood samples which were studied at the same time by the micromixing technic described indicates that the microtechnic was much more rapidly and easily performed and was of comparable accuracy. One can perform three to six micro P50 determinations in the time it takes to perform one classic tonometry determination using three to four points on the curve.

Since our first report (Astrup, 1969) at a symposium in Uppsala in February 1969 on changes of the oxygen affinity of hemoglobin due to pH-dependent 2,3-DPG changes we have studied this relationship more extensively in patients with acid-base disorders and also in normal individuals with induced changes of the acid-base status of the blood. The results of these investigations will be presented in this paper.

Red cell pH was calculated in human maternal and fetal blood, from plasma pH and the distribution of isotopically labelled 2,5-dimethyl-2,4-oxazoladine dione (DMO). Results show a significant difference, at the same plasma pH, in the red cell pH's of maternal and fetal blood. The difference is in a direction which would reconcile differences observed in oxyhemoglobin dissociation functions of human maternal and fetal whole bloods, and the absence of such differences when maternal and fetal hemoglobin solutions are studied in buffers of the same ionic concentration. The relationship of this observation to the role of DPG and ATP in determining dissociation function is discussed.

Ten dogs were made progressively hypoxic by rebreathing from an air-filled spirometer. Arterial blood samples were drawn at five levels of alveolar Po2 (100, 70, 55, 40, and 25 mm Hg), as well as samples before and after the hypoxia for O2-capacity determinations. Half the animals then were given 25 ml/kg of fat emulsion intravenously and the others were given the same amount of dextran. The same sampling procedure was repeated and the blood was analyzed for O2 content. In separate experiments, the same procedure was followed for five dogs but only fat emulsion was given and the arterial blood was analyzed for Po2 and Pco2. Oxyhemoglobin dissociation curves were constructed from the values of saturation at progressively falling alveolar o2. These were transformed into a linear equation by the Hill equation and treated statistically. No significant differences were found between any of the comparisons of slope or displacement. It was concluded that lipemia offered no practical hindrance to the uptake of O2 by the red cell. Alveolar-arterial gas tension differences revealed no change after intravenous fat emulsion in the Po2 difference, but there was a threefold increase in the Pco2 difference. Submitted on June 12, 1961