Introduction Previous studies have shown through theoretical analyses that the ratio of the partial pressure of oxygen in arterial blood (PaO 2 ) to the inspired oxygen fraction (FiO 2 ) varies with the FiO 2 level. The aim of the present study was to evaluate the relevance of this variation both theoretically and experimentally using mathematical model simulations, comparing these ratio simulations with PaO 2 /FiO 2 ratios measured in a range of different patients.

This article describes a mathematical model of the acid-base chemistry of blood. The model is formulated from first principles by considering the "components" of blood and the reaction equations in the plasma and erythrocyte fractions. Equations are formulated to describe the total concentration of blood components, the physicochemical properties, and the equilibrium position of reactions. The model includes 28 equations and 12 parameters. All equations can be solved from six variables included in the model. The model uses simple mathematics, without introducing intermediate concepts or linear coefficients necessary for algebraic solution. Model equations are solved simultaneously using numerical methods. Model parameters are estimated and the model verified for plasma, fully oxygenated blood, and deoxygenated blood. Published data are used to estimate model parameters and normal conditions and to verify model simulations. The model reproduces experimental results, including addition or removal of CO2, or strong acid to plasma; CO2, strong acid or haemoglobin to blood; and the effects of deoxygenating blood. The model can also be used as the basis for models of whole body CO2 transport as illustrated in the accompanying article. As such, it is possible to simulate the effects on blood of physiological changes in ventilation or metabolism.

Apolipoprotein (apo) A-I is the principal protein component of the plasma high density lipoproteins (HDLs). Tissue culture studies have suggested that lipid-free apo A-I may, by recruiting phospholipids (PLs) and unesterified cholesterol from cell membranes, initiate reverse cholesterol transport and provide a nidus for the formation, via lipid-poor, pre-beta-migrating HDLs, of spheroidal alpha-migrating HDLs. Apo A-I has also been shown to inhibit hepatic lipase (HL) and lipoprotein lipase (LPL) in vitro. To further study its functions and fate in vivo, we gave lipid-free apo A-I intravenously on a total of 32 occasions to six men with low HDL cholesterol (30 to 38 mg/dL) by bolus injection (25 mg/kg) and/or by infusion over 5 hours (1.25, 2.5, 5.0, and 10.0 mg.kg-1.h-1). The procedure was well tolerated: there were no clinical, biochemical, or hematologic changes, and there was no evidence of allergic, immunologic, or acute-phase responses. The 5-hour infusions increased plasma total apo A-I concentration in a dose-related manner by 10 to 50 mg/dL after which it decreased, with a half-life of 15 to 54 hours. Coinfusion of Intralipid reduced the clearance rate. The apparent volume of distribution exceeded the known extracellular space in humans, suggesting extensive first-pass clearance by one or more organs. No apo A-I appeared in the urine. Increases in apo A-I mass were confined to the pre-beta region on crossed immunoelectrophoresis of plasma and to HDL-size particles on size exclusion chromatography. Increases were recorded in HDL PL, but not in HDL unesterified or esterified cholesterol. Increases also occurred in LDL PL and in very low density lipoprotein cholesterol, triglycerides, and PL but not in plasma total apo B concentration. These results can all be explained by combined inhibition of HL and LPL activities. Owing to the effects that this would have had on HDL metabolism, no conclusions can be drawn from these data about the role of lipid-free apo A-I in the removal of PL and cholesterol from peripheral tissues in humans. The kinetic data suggest that the fractional catabolic rate of lipid-free apo A-I exceeds that of spheroidal HDLs and is reduced in the presence of surplus PL.

No abstract

Pulmonary gas exchange can be described equally well using non-invasive data. The simplicity of the non-invasive approach makes the method suitable for large-scale clinical use.

Background Arterial oxygenation is often impaired during one-lung ventilation, due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5 ml/kg predicted body weight) in the context of a lung-protective approach exacerbates atelectasis. This study sought to determine the combined physiologic effects of positive end-expiratory pressure and low VT during one-lung ventilation. Methods Data from 41 patients studied during general anesthesia for thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O during bilateral lung ventilation and one-lung ventilation and, subsequently, during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory pressure. Shunt fraction and high V/Q were measured using variation of inspired oxygen fraction and measurement of respiratory gas concentration and arterial blood gas. The level of positive end-expiratory pressure was applied in random order and maintained for 15 min before measurements. Results During one-lung ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11% (5 to 16), respectively (P < 0.001). The Pao2/Fio2 ratio increased significantly only at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). Driving pressure decreased from 16 ± 3 cm H2O at a positive end-expiratory pressure of 0 cm H2O to 12 ± 3 cm H2O at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). The high V/Q ratio did not change. Conclusions During low VT one-lung ventilation, high positive end-expiratory pressure levels improve pulmonary function without increasing high V/Q and reduce driving pressure.

The venous values of pH, corrected for bias, can give arterial values which are within reasonable laboratory and clinical acceptance criteria. For PCO2 this is also true, except for peripheral blood, where the standard deviation is outside laboratory acceptance criteria but within clinical acceptance criteria. For PO2 the arteriovenous differences are not randomly distributed and even for PO2

The system illustrates how mathematical models combined with decision theory can aid in the difficult compromises necessary when deciding on ventilator settings.