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Biomedical subjects

F Kreuzer

Publications and source records attributed to F Kreuzer.

At least 19 recordsLinked to original sources

Effect of metabolic acidosis on pulmonary gas exchange of artificially ventilated dogs.

It is well established that metabolic acidosis induces a reduction in alveolar-arterial O2 difference [(A-a)Do2] in artificially ventilated dogs by shifting the oxyhemoglobin dissociation curve (ODC) and/or by improving the distribution of the ventilation-to-perfusion ratio (VA/Q) throughout the lung. To assess the influence of these two factors we examined eight artificially ventilated dogs before and after induction of metabolic acidosis by a perfusion of 0.3 mol HCl. We measured classic indexes of cardiopulmonary function. VA/Q distribution was estimated using the multiple inert gas elimination technique (MIGET). ODC and Bohr effect of each dog were obtained by a dynamic method. Acidosis increased CO2 excretion, respiratory quotient, blood PO2 at 50% saturation, and arterial PCO2 and PO2 with a simultaneous decrease in (A-a)DO2. In seven dogs, the distribution of VA and Q, as assessed by MIGET, was not substantially modified by HCl perfusion. In the eighth dog the distribution of Q and VA became more homogeneous after acidosis. This led us to conclude that the Bohr effect is the most important and most consistently observed factor responsible for the decrease in (A-a)DO2 found in metabolic acidosis. In rare cases the increase in pulmonary arterial pressure may complement this action by improving the distribution of the VA/Q ratio.

Acidosis

Reestimation of the effects of inorganic phosphates on the equilibrium between oxygen and hemoglobin.

In a previous paper, published in this journal, we showed that the data obtained in patients with severe ketoacidosis suggest that inorganic phosphates (K2HPO4) can increase their P50 and therefore enhance tissue oxygenation without concomitant alteration of the 2,3 diphosphoglycerate (DPG). In order to test the hypothesis that K2HPO4 could influence the oxyhemoglobin dissociation curve (ODC) by a mecanism which was not DPG mediated we have measured the total ODC on whole blood with and without addition of 13-80 mmol/l of inorganic phosphates. On average, the level of DPG remained unchanged when the P50 with K2HPO4 was significantly higher (p greater than 0.001) (P50 = 29.9 +/- 3.7 mmHg) than when phosphates were not administered (P50 = 25.5 +/- 2.8 mmHg). The relationship between P50 (mmHg) and K2HPO4 (= X mmol/l) was delta P50 = -2.97 10(-3)(X)2 +0.26(X)-0.42 (r = 0.78). Seeing that phosphates have an immediate action on the ODC, we calculated in our ketoacidosis patients, the relationship between the P50, the inorganic phosphates (P(i) in mg%) and the DPG in mumol/gHb. Both factors exert a highly significant effect (p less than 0.001) on the P50, according to the following equation: P50 = 0.35 DPG +0.26 P(i) + 18.92 (r = 0.73). Our data are important in two points. First it is useful to add inorganic phosphates to the treatment of patients with severe ketoacidosis in order to enhance their tissue oxygenation. Second they recall that the ODC is not only determined by the classical effects of temperature, pH and DPG but also by inorganic anions, like phosphates as described by Benesh and Benesh in their pioneering work.

2,3-Diphosphoglycerate

Computed myocardial PO2 histograms: effects of various geometrical and functional conditions.

A model of myocardial oxygenation was developed that allows calculation of Po2 histograms under varying conditions. The model consists of parallel tissue cylinders with varying radii, simulating the heterogeneity of capillary spacing, in agreement with our previous experimental results. The facilitated diffusion of O2 by myoglobin, an additional resistance to diffusion at the capillary level, and the Michaelis-Menten type of O2 consumption were also incorporated. The shape of the histograms depends on input data. When no additional barrier to O2 transport is included, the histograms resemble those obtained with Po2 surface electrodes, and they are strongly dependent on heterogeneity in capillary spacing and capillary blood flow. On the other hand, an inclusion of an additional capillary barrier combined with the Michaelis-Menten type of O2 consumption can generate Po2 histograms similar to those derived from myoglobin cryospectroscopy. In this case, the Po2 histograms are relatively independent of heterogeneity of capillary spacing and blood flow. The facilitation of O2 diffusion by myoglobin has only a modest effect on the form of the histograms in all situations considered.

Animals

Hypoxic ventilatory response of rats born at simulated altitude.

Steady-state ventilatory response to isocapnic hypoxia was measured in awake rats: a) resident at sea level (Control); b) born at sea level and acclimatized to a simulated altitude of 3500 m (Newcomers); c) born and raised for two generations at a simulated altitude of 3500 m (HA-II Generation). Arterial PO2, PCO2, and pH were measured at the same time as ventilation. Resting ventilation (mean +/- SE) on room air in Control, Newcomers, and HA-II Generation was 707 +/- 25, 811 +/- 28 and 878 +/- 21 ml.min-1.kg-1, respectively. The ratios of ventilations measured at PaO2 55 and 100 Torr were 1.61 for Control, 1.52 for Newcomers, and 1.60 for HA-II Generation and were not significantly different from one another. The ventilatory response to 5% CO2 in air was also similar in all three groups. After four days at sea level, ventilatory responses of HA-II Generation to normoxia or isocapnic hypoxia were the same as those of sea level control. We conclude that the HA-II Generation groups had ventilatory responses to hypoxia that did not differ from those of Newcomers acclimatized to the same altitude. Unlike man, rats that were born and raised at altitude for two generations did not show any "blunting" of the ventilatory response to hypoxia.

Altitude

Muscle oxygen tension, hemodynamics, and oxygen transport after extracorporeal circulation.

In eight patients who underwent elective coronary bypass operation, skeletal muscle PO2 was measured with a polarographic needle electrode as an index of peripheral tissue perfusion to study recovery after extracorporeal circulation. Measurements of skeletal muscle PO2 and O2 supply to the tissues were obtained immediately after ICU admission and after 2, 4, 8, and 16 h. During the first 2 h, mean arterial BP was high, mixed venous PO2 decreased, the arteriovenous O2 difference increased, and skeletal muscle PO2 decreased. The P50 of the O2 dissociation curve on ICU admission was decreased and thereafter increased to a maximal value at 8 h, and normalized again after 16 h. After the initial decrease, the median of the skeletal muscle PO2 returned to normal values, but decreased again after 16 h. The results showed that, during the first 4 h postoperatively, microcirculatory changes occurred despite normal cardiovascular and respiratory variables.

Aged

Determination of permeabilities for two gases from recording the partial pressure of one gas.

When a flexible diffusion layer separates two closed gas chambers containing different mixtures of several gases, the different permeabilities of the layer for these gases lead to differences in the total gas pressures of the two chambers resulting in bulging of the layer and consequent changes in the chamber volumes. Application of the gas laws to binary gas mixtures provides two equations relating the partial pressure changes of one gas in any of the two chambers to the partial pressure difference between the two chambers across the layer. This permits the calculation of the two unknown factors, permeability (or Krogh's diffusion coefficient) of the layer for the measured gas and the permeability ratio of the two gases. Thus the permeabilities of both gases can be determined from recording the partial pressure of one of the gases only. We filled the gas chambers with different mixtures of oxygen and a second gas (nitrogen or carbon dioxide) at atmospheric pressure, closed the chambers, and measured the diffusion of the gases across thin (12-500 microns) layers of various materials by recording the oxygen partial pressure in both chambers with polarographic oxygen electrodes. Permeabilities of these layers for oxygen and the other gas were determined for plastic layers (MEM213, Silastic, Teflon), as well as water and methemoglobin solutions either in a fluid layer or soaked in Millipore filters. The data agreed well with those obtained from other studies in most cases.

Gases

Facilitated carbon dioxide transport in bovine albumin solutions.

Steady-state CO2 diffusion in the presence of a CO2 gradient was measured in thin layers of bovine albumin solutions containing different amounts of buffer base, added as NaHCO3, and/or of NaCl. In the same solutions, electrical potentials due to the CO2 diffusion across the layers were measured. Addition of carbonic anhydrase induced a chemical reaction equilibrium to exist for the CO2 reaction system, and led to equilibrium values for facilitated CO2 transport due to a bicarbonate flux and to maximum values for the diffusion potential. The diffusion potentials are generated due to the large differences in the ionic mobilities of albumin and other ionic species such as bicarbonate. The diffusion potential markedly reduces the facilitated CO2 flux. The presence of sodium chloride had no significant effect on the CO2 transport rate. The total mass transfer rates of CO2 in albumin solutions were considerably lower than those found by Stroeve and Ziegler (23) in hemoglobin solutions at identical concentrations of buffer base.

Albumins

Regulation of the peripheral vasculature and tissue oxygenation in health and disease.

The evidence has become convincing that in certain critical illnesses such as ARDS, there is pathologic disturbance in O2 delivery to the tissues. This disturbance is marked by an abnormal dependency of O2 uptake upon total O2 delivery. Although this has been attributed to mitochondrial dysfunction in the past, current belief is that such apparent dysfunction is secondary to derangement of the microcirculation that causes an impairment in tissue oxygenation. Microembolization and other disturbances in the local regulation of perfusion have been postulated to be responsible for this derangement. The net effect is to increase the diffusion pathway for oxygen from the tissue capillary. Our ability to deal conceptually with this kind of alteration in tissue oxygenation is dependent upon the mathematical model that is applied. We have discussed two generic models for tissue oxygenation to show the constraints imposed upon quantifying the effects of alteration in any single factor upon tissue PO2. The salient factor that has emerged is that creation of greater than normal heterogeneity in flow or its distribution in the peripheral microcirculation has the inevitable consequence of making tissue hypoxic.

Animals

The effect of blood O2 affinity on the efficiency of O2 transport in blood at hypoxic hypoxia.

An index of the efficiency of O2 transport in blood and delivery to tissues, the capacitance coefficient beta, was theoretically analyzed as a function of the position of the blood O2 dissociation curve (ODC). The P50 at which beta reaches its maximum is high at normoxia and decreases with lowering the ambient PO2. At very deep hypoxia this value becomes lower than the normal P50 of human blood. An increase of blood O2 capacity enlarges beta, particularly at deep hypoxia, and also increases the P50 at which maximal beta is reached. Changes of (a-v)O2 have ambivalent effects, depending on both P50 and PaO2. The capacitance coefficient beta was further calculated as a function of PaO2 at three values of P50, simulating the effect of a shift of the ODC. The capacitance coefficient is several times higher at deep hypoxia than at normoxia at all values of P50 used. A shift of the ODC to the left results in a moderate decrease of beta at mild hypoxia but in a large increase at severe hypoxia; a shift to the right has a reverse effect.

Animals