Abnormal hemoglobin oxygen affinity and the coronary circulation.
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Biomedical subjects
Publications and source records attributed to B Teisseire.
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The polymerization of hemoglobin for use as a blood substitute and an oxygen carrier would be of interest because high-mol. wt macromolecules would have a longer vascular retention time than the monomer. We found that the molecules resulting from the treatment of hemoglobin with ethyldimethylaminopropylcarbodiimide did not have a higher mol. wt than free hemoglobin and also had a dissociation curve resembling that of monomers, but seemed more stable.
1. Oxygen-linked carbamino formation in fetal erythrocytes was compared to that measured in adult erythrocytes. 2. Whole oxygen binding curves were recorded on washed intact erythrocytes either fresh or D-glycerate-2,3-P depleted with a continuous recording technique. Erythrocytes were resuspended in buffer media of different pH and PCO2 varying from 0-10.7 kPa (80 torr) at physiological ionic strength. Oxygen linked carbamates were estimated as deltalog PO2/delta log PCO2 at constant pH and constant saturation levels from 10-90% oxygen saturation. 3. The overall CO2 effect (deltalog P50/deltalog PCO2) was consistently lower in fetal erythrocytes than in the adult. The deltalog PO2/deltalog PCO2 ratio was markedly dependent on oxygen saturation in both types of erythrocytes and highest at the early part of the oxygen binding curve. This was more so in fetal erythrocytes. 4. Carbamino formation was lower in fetal erythrocytes than in adult erythrocytes at any pH value, indicating a higher apparent pK of the alpha amino groups involved in CO2 binding in fetal erythrocytes. This may be related to the different primary structures of the non alpha chains of HbFII and HbAI. 5. The large effect of low PCO2 on both fetal and adult erythrocytes was related to the higher affinity for CO2 of deoxyhemoglobin compared to oxyhemoglobin and a model for CO2 binding analogous to that described by de Bruin et al. [6] for anion binding is proposed. 6. It is concluded that the lower CO2 binding to fetal erythrocytes is in keeping with the lower allosteric effect of other major effectors of hemoglobin within the cells. This leads to a higher affinity for O2 of fetal erythrocytes well suited for O2 transport in utero.
The hemodynamic and respiratory effects of spontaneous ventilation with continuous positive airway pressure (CPAP) and mechanical ventilation with positive and expiratory pressure (CPPV) were compared in six patients with acute respiratory failure. Arterial and mixed venous gases, cardiac output, oxygen delivery and consumption, airway and oesophageal pressures were measured, with each patient on intermittent positive pressure ventilation (IPPV), CPAP and CPPV with the same level of positive and expiratory pressure (PEEP = 20 cmH2O). CPAP was as efficient as CPPV for improving arterial oxygenation. Cardiac output was higher on CPAP than on CPPV due to a lower intra-thoracic pressure with spontaneous ventilation, thus oxygene transport was higher with this methode. However total oxygene consumption and PaCO2 were slightly increased with CPAP due to a higher breathing's work. So, CPAP is as efficient as CPPV at the same level of PEEP in improving intra-pulmonary shunt and PaO2, without adversely affecting cardiac output.
The effect of an increase in hemoglobin O2 affinity on myocardial O2 delivery was studied in a blood perfused working rat heart preparation. In a first series of experiments P50 (PO2 for which saturation is 50%) was lowered by use of carbon monoxide. The heart was alternatively perfused with the blood sample of P50 = 32 mm Hg and the blood sample of P50 = 17 mm Hg. O2 capacity of both samples was kept the same by appropriate hemodilution. In a second serie of experiments change of P50 was obtained by the use of adult human erythrocytes containing hemoglobin creteil with a P50 of 13.6 mm Hg. As P50 decreased from 25 to 10 mm Hg, coronary sinus PO2 (PcsO2) diminished from 26 +/- 2 to 18 +/- 2 mm Hg (-29 +/- 2%), coronary sinus O2 content (CcsO2) increased by 15 +/- 3%, myocardial oxygen consumption did not change significantly. The percentage of increase of coronary flow was 23 +/- 4%. Analysis of these results with a simple mathematical model of O2 delivery suggest that increase in HbO2 affinity is corrected by a simultaneous increase in coronary flow and capillary recruitment.
Septic shock associated with depressed myocardial function generally requires the use of catecholamine. Currently dopamine is often selected. Dobutamine is a newly developed catecholamine which has been shown to be of value in severe cardiomyopathic disease. The aim of this work was to determine the most appropriate drug by comparing haemodynamic responses to dopamine and dobutamine in 19 studies carried out in 11 patients with septic shock and heart failure. Cardiac index increased siliarly with dopamine and dobutamine (33%), as did stroke volume (respectively 26.4 and 25%). Arterial pressure increased by 17% with dopamine whereas it did not significantly change with dobutamine due to reduction in vascular resistance of 19%. Dobutamine decreased filling pressure, either right (14%) of left (28%) whilst they slightly but unsignificantly increased with dopamine. Pulmonary shunting increased more with dopamine (47%) than with dobutamine (16%), but PaO2 remained constant with both. Since septic shock is characterized by lowered arterial pressure and vasodilatation it is concluded that effects of dopamine on capacitance and resistance vessels make this drug more suitable. In addition it selectively increases renal blood flow. Nevertheless dobutamine could be appropriate, in case of very high filling pressures, severe peripheral vasoconstriction, marked pulmonary shunting and in some cases where dopamine becomes ineffective.
Ten patients, suffering from severe viral or bacterial pneumonia had circulatory shock, characterised haemodynamically by normal or high cardiac output (CI = 4.1 +/- 1.2 1/min/m2) and low systemic resistance (SVR = 14 +/- 3.7 mm Hg/1/min/m2). Existence of such a hyperkinetic state greatly complicates the management of patients. Plasma volume expansion, performed in five cases of initial hypovolaemia, and Dopamine infusion (five patients) increased markedly the intra-pulmonary shunting. High level PEEP ventilation was not tolerated, despite the improvement of blood gases it produced. Extra-corporeal membrane lung oxygenation (three cases), whilst giving an initial decrease of shunting and restoring SVR, produced no long term surviors. All ten patients died from intractable shock and severe hypoxaemia. Spontaneous ventilation with positive expiratory pressure (CPAP) is believed to be an attractive alternative, due to its absence of deleterious haemodynamic effects.
1. We have observed that the alkaline Bohr effect of washed human fetal erythrocytes was larger than in human adult intact red cells, in physiological conditions of pH, PCO2 and temperature. This was also observed independently of the presence of CO2 and of 2,3 diphosphoglycerate (fresh or stored erythrocytes). 2. Experiments performed in purified HbFII and HbA1 solutions and direct titration of protons released upon oxygenation confirmed the larger alkaline Bohr effect of fetal hemoglobin, at physiological ionic strength. 3. At low chloride concentration HbFII solutions had an alkaline Bohr effect identical to that measured in HbA1 solutions. 4. Titration of purified Hb solutions with increasing concentrations of NaCl evidenced a lower O2 linked chloride binding by HbFII and predominantly at acid pH. 5. It is concluded that the larger alkaline Bohr effect of fetal erythrocytes of HbFII solutions is related to a diminished acid Bohr effect, due to the lower affinity of HbFII for chloride anions. 6. The physiological interest of these results for placental O2 transfer (double Bohr effect) and O2 delivery to the foetus is discussed.
The first (delta S/delta P) and second (delta 2S/delta [H+] delta P) partial derivatives of hemoglobin saturation with respect to oxygen pressure and [H+] were numerically calculated for the blood of non-smoking young adult at different pH, PCO2 and [2.3-DPG]. Their functional value in respiratory physiology was stressed.
Hemoglobin Hb) Creteil alpha2beta(2)89 (F5) Ser leads to Asn is a high oxygen-affinity variant that has a low cooperativity, a decreased Bohr effect, and does not interact with diphosphoglycerate (DPG) (1). This hemoglobin variant was silent by routine electrophoresis. Careful analyses of the oxygen dissociation curves of erythrocytes, determined at varying pH and Pco2 in fresh and DPG-depleted cells, gave extensive information on the abnormal function of the mutant hemoglobin. From the O2 dissociation curves of the erythrocytes of the heterozygous subject it appeared that Hb Creteil is inappropriate for O2 transport to the tissues because it remained completely saturated with O2 at normal physiologic levels of Po2. In-vivo measurements showed that only one half of the total hemoglobin present actually participated in oxygen transport. Polycythemia should therefore be maintained within clinically tolerable limits because it helps to keep arterial Po2 and Pvo2 close to their normal values and thus protects the individual from a permanent increase in blood flow.
In patients with fulminating pulmonary edema not responsive to conventional therapy, venoarterial membrane lung bypass can provide assistance if decreased systemic blood pressure prevents use of high-level positive end-expiratory pressure ventilation. In 10 patients with acute respiratory failure, partial venoarterial bypass provided a rapid and marked improvement of systemic oxygenation. Measurement of pulmonary blood flow (PBF) and intrapulmonary shunting (QS/QP) during bypass via prolonged left heart catheterization showed that left ventricular PaO2 was increased through a rapid and profound reduction of QS/QP. During the first days of bypass, derecruitment of pulmonary vessels is probably the mechanism of improved pulmonary oxygenation. When low pulmonary arterial pressures (PAP) are sustained, resorption of pulmonary edema is favored. Despite the beneficial effects of bypass, death occurred in every case due to diffuse interstitial fibrosis and/or parenchymal damage. The absence of healing, due to prolonged circulatory exclusion, may be detrimental despite immediate improvement. Because of this possibility, venovenous or mixed perfusion should be more extensively explored.
The Haemodynamic response to dopamine infusion has been assessed in 30 patients in septic shock with myocardial dysfunction. Dopamine infusion resulted in a haemodynamic improvement as indicated by significant increases in cardiac output of 38.4% (p less than .001), stroke volume 18.7% (p less than .001), and mean arterial pressure of 33% (p less than .001). Despite the inotropic effect, left ventricular filling pressure did not change in 20 cases and increased in 10 cases. Mean peripheral resistance remained unchanged with a scatter of individual responses depending upon factors such as dopamine dose and initial vascular resistance. Dopamine increased intrapulmonary shunting by 48% (p less than .001), insignificantly decreased PaO2, increased mixed venous oxygen saturation by 16% (p less than .02) and decreased pulmonary vascular resistance by 15% (p less than .02). Both isoprenaline and dopamine improve stroke volume by an inotropic action, with an increase in venous return in the case of the latter and a reduction in afterload in the former. It is concluded that the usefulness of dopamine in septic shock may be limited in patients with previous myocardial disease because of the risk of increasing preload and in hypoxaemic patients because of the risk of increasing intrapulmonary shunting.
In vitro studies of a stroma free haemoglobin solution of human origin (Wx B 8326, Warner-Lambert) in comparison with fresh and stored low DPG whole human blood, was undertaken with regard to the fixation. of oxygen. Such an hemoglobin solution was shown to exhibit a high affinity for oxygen and a low Bohr effect (assessed from the delta log Po2/delta pH ratio). The specific effect of Co2 (assessed from the delta log Po2/delta log. Pco2 ratio) appeared to be increased as compared to fresh whole blood. This hemoglobin solution was tested as a blood substitute in two in vivo experimental situations: exsanguino transfusion on rabbits (n = 6) and closed-chest extracorporeal circulation on dogs (n = 6). In order to evaluate the part taken by the tested Hb solution in arterial O2 carrying capacity and in O2 delivery, two ratios were calculated: arterial plasmatic O2 content/arterial circulating blood O2 content and arterio-venous plasmatic O2 difference/arterio-venous circulating blood O2 difference. These two ratios amounted 28,2 +/- 2,5% (rabbits) and 47,0 +/- 6% (dogs) for the arterial O2 carrying capacity and 13,8 +/- 3,0% (rabbits) and 25,8 +/- 5,0% (dogs) for the tissular O2 delivery. Among the properties of the tested stroma free hemoglobin solution its low contribution to the tissular O2 delivery, its high affinity for oxygen, its low Bohr effect and its short half-life as compared to whole blood are not favouring its use in clinical practice.
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We describe a method for perfusion of a working isolated rat heart with washed erythrocytes suspended in a Krebs-Henseleit bicarbonate buffer containing bovine albumin (fraction V). With washed pig red cells, as hematocrit was varied between 0 and 40%, coronary flow (CF), aortic flow (AF), external work (W), and myocardial oxygen consumption (MVO2) were measured. Hemodynamic data at a hematocrit of 30% (CF = 5.4 +/- 0.7 ml/min per g, AF = 75 +/- 8 ml/min per g) were identical with those reported for the intact animal. Coronary sinus PO2 was highest with a red cell-free perfusate suggesting that coronary flow is partially shunted. Human red cells obtained from banked blood, were tried also with success. With careful filtration, the preparation is stable for 2 h and well suited for study of the dynamics of myocardial oxygen delivery.