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Biomedical subjects

S E Rees

Publications and source records attributed to S E Rees.

15 recordsLinked to original sources
PubMed2006

Using physiological models and decision theory for selecting appropriate ventilator settings.

OBJECTIVE: To present a decision support system for optimising mechanical ventilation in patients residing in the intensive care unit. METHODS: Mathematical models of oxygen transport, carbon dioxide transport and lung mechanics are combined with penalty functions describing clinical preference toward the goals and side-effects of mechanical ventilation in a decision theoretic approach. Penalties are quantified for risk of lung barotrauma, acidosis or alkalosis, oxygen toxicity or absorption atelectasis, and hypoxaemia. RESULTS: The system is presented with an example of its use in a post-surgical patient. The mathematical models describe the patient's data, and the system suggests an optimal ventilator strategy in line with clinical practice. CONCLUSIONS: The system illustrates how mathematical models combined with decision theory can aid in the difficult compromises necessary when deciding on ventilator settings.

Carbon Dioxide↗
PubMed2006

Reproduction of MIGET retention and excretion data using a simple mathematical model of gas exchange in lung damage caused by oleic acid infusion.

The multiple inert-gas elimination technique (MIGET) is a complex mathematical model and experimental technique for understanding pulmonary gas exchange. Simpler mathematical models have been proposed that have a limited view compared with MIGET but may be applicable for use in clinical practice. This study examined the use of a simple model of gas exchange to describe MIGET retention and excretion data in seven pigs before and following lung damage caused by oleic acid infusion and subsequently at different levels of positive end-expiratory pressure. The simple model was found to give, on average, a good description of MIGET data, as evaluated by a chi(2) test on the weighted residual sum of squares resulting from the model fit (P > 0.2). Values of the simple model's parameters (dead-space volume, shunt, and the fraction of alveolar ventilation going to compartment 2) compared well with the similar MIGET parameters (dead-space volume, shunt, log of the standard deviation of the perfusion, log of the standard deveation of the ventilation), giving values of bias and standard deviation on the differences between dead-space volume and shunt of 0.002 +/- 0.002 liter and 7.3 +/- 2.1% (% of shunt value), respectively. Values of the fraction of alveolar ventilation going to compartment 2 correlated well with log of the standard deviation of the perfusion (r(2) = 0.86) and log of the standard deviation of the ventilation (r(2) = 0.92). These results indicate that this simple model provides a good description of lung pathology following oleic acid infusion. It remains to be seen whether physiologically valid values of the simple model parameters can be obtained from clinical experiments varying inspired oxygen fraction. If so, this may indicate a role for simple models in the clinical interpretation of gas exchange.

Animals↗
PubMed2006

Oxygenation within the first 120 h following coronary artery bypass grafting. Influence of systemic hypothermia (32 degrees C) or normothermia (36 degrees C) during the cardiopulmonary bypass: a randomized clinical trial.

BACKGROUND: Lung function is often impaired after cardiac surgery performed under cardiopulmonary bypass (CPB). Normothermic CPB has become more common, but it remains unknown whether it reduces post-operative lung function compared with hypothermic CPB. The aim of this study was to investigate oxygenation within the first 120 h after systemic hypothermia and normothermia under CPB. METHODS: Thirty patients undergoing coronary artery bypass grafting (CABG) were randomized to either hypothermic (32 degrees C) or normothermic (36 degrees C) CPB. Oxygenation was studied by a simple method for the estimation of intrapulmonary shunt and ventilation-perfusion (V/Q) mismatch pre-operatively and 4, 48 and 120 h post-operatively by changing Fio2 in four to six steps. V/Q mismatch was described with DeltaPo2 (normal values, 0-2.38 kPa). RESULTS: Shunt and V/Q mismatch (DeltaPo2) increased post-operatively in both groups (P<0.01), with no differences between the groups, and with the nadir values 48 h after surgery, i.e. shunt of 15% (5.8-25%) and DeltaPo2 of 3.0 kPa (0.8-14 kPa) [values given as median (range)]. CONCLUSIONS: Impaired oxygenation is prevalent and prolonged following CABG, with equal intensity after hypothermic and normothermic CPB.

Adult↗
PubMed2005

A method for calculation of arterial acid-base and blood gas status from measurements in the peripheral venous blood.

In non-emergency medical departments such as internal medicine sampling of arterial blood and analysis for acid-base status is not routinely performed. Peripheral venous blood is routinely taken but interpretation of its acid-base status is difficult. This paper presents a method for calculation of arterial acid-base and blood gas status from measurements in peripheral venous blood combined with a pulse oximeter measurement of arterial saturation. The use of the method has been illustrated using the data of three patients with different acid-base, haemodynamic, and metabolic conditions. The sensitivity of the method has been tested for measurement errors including venous blood acid-base and blood gas status and pulse oximetry; errors due to physiological assumptions including the values of RQ and strong acid production at the tissues; and errors due to air bubbles in the blood. Errors due to these effects are relatively insignificant except for errors in calculated arterial PO(2), particularly when SpO(2) is greater than 97%; and errors when the change in base excess across the sampling site due to strong acid production is greater that 1.3 mmol/l.

Acid-Base Equilibrium↗
PubMed2005

Mathematical models of oxygen and carbon dioxide storage and transport: the acid-base chemistry of blood.

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.

Acid-Base Equilibrium↗
PubMed2005

Mathematical models of oxygen and carbon dioxide storage and transport: interstitial fluid and tissue stores and whole-body transport.

This article describes a mathematical model of whole-body O2 and CO2 transport. The model includes representation of the acid-base chemistry of the blood, interstitial fluid, and tissues, plus transport of O2 and CO2 between compartments representing tissues, interstitial fluid, arterial and venous blood, and lungs. The model includes equations for calculation of all concentrations in the compartments, including equations describing the physicochemical properties and reaction equations of interstitial fluid and tissues. In addition, the model includes equations that describe the flow of substrate between the compartments and differential equations allowing calculation of the changes in state variables caused by the flow of substrates between the compartments. This model is designed to calculate the effects of metabolic and respiratory perturbations, such as variation in breathing pattern or production of strong acid at the tissues. The model reproduces the results of published experiments when used to simulate (1) normal conditions in the lungs, arterial and venous blood, interstitial fluid, and tissues during normal ventilation; (2) the characteristic two-exponential response to changes in minute ventilation; and (3) the relationship between arterial blood values of PCO2 and HCO3,p during inspiration of different fractions of CO2.

Acid-Base Equilibrium↗
PubMed2004

Hypoxaemia after cardiac surgery: clinical application of a model of pulmonary gas exchange.

BACKGROUND AND OBJECTIVE: To investigate the clinical application of a mathematical model of pulmonary gas exchange, which ascribes hypoxaemia to shunt and ventilation/perfusion mismatch. Ventilation/perfusion mismatch is quantified by deltaPO2, which is the drop in oxygen pressure from alveoli to lung capillaries. Shunt and deltaPO2 were used to describe changes in oxygenation after coronary artery bypass grafting. METHODS: Fourteen patients were studied 2-4 h after surgery and on postoperative days 2, 3 and 7. On each occasion inspired oxygen fraction was changed in four to six steps to obtain arterial oxygen saturation (SaO2) in the range of 90-100%, enabling construction of FEO2/SaO2 curves. Measurements of ventilation, circulation and oxygenation were entered in a previously described mathematical model of pulmonary gas exchange. RESULTS: We found that oxygenation was most impaired 3 days after surgery. By fitting the mathematical model to the FEO2/SaO2 curve, we found that shunt remained constant throughout the study period. However, deltaPO2 increased from 0.5 kPa (median, range 0-3.8) 2-4 h after surgery, to 3.2 kPa (range 1.2-6.4, P < 0.05) on day 2, and to 4.0 kPa (range 1.2-8.3) on day 3. On day 7, deltaPO2 decreased to 2.2 kPa (range 0-3.5, P < 0.05). CONCLUSIONS: Ventilation/perfusion mismatch (deltaPO2), rather than shunt, explains the changes in postoperative oxygenation. The model of pulmonary gas exchange may serve as a useful and potentially non-invasive clinical tool for monitoring patients at risk of postoperative hypoxaemia.

Aged↗
PubMed2001

Modelling of hypoxaemia after gynaecological laparotomy.

BACKGROUND: Late postoperative arterial hypoxaemia is common after major surgery, and may contribute to cardiovascular, cerebral or wound complications. This study investigates the time course of hypoxaemia following gynaecological laparotomy, and estimates parameters of mathematical models of pulmonary gas exchange to describe hypoxaemia. METHODS: Twelve patients were studied on four occasions; preoperatively, 2, 8 and 48 h after surgery. On each occasion inspired oxygen fraction (FIO2) was varied, changing end-expired oxygen fraction (FEO2) to achieve arterial oxygen saturations (SaO2) ranging from 90% to 100%. Measurements of ventilation and blood gases were taken. Oxygenation was characterized plotting FEO2 against SaO2. The shape and position of the FEO2/SaO2 curve was described using two mathematical models including parameters describing gas exchange: either shunt and resistance to oxygen diffusion (Rdiff); or shunt and asymmetry of ventilation-perfusion (fA2). RESULTS: Two hours after surgery SaO2 was reduced from 97.5%+/-1.2% (mean+/-SD) to 93.8%+/-2.7% (mean+/-SD) (P<0.001). Values of shunt, Rdiff and fA2 were significantly changed at 2 and 8 h postoperatively. Forty-eight hours postoperatively Rdiff and fA2 were still significantly changed. CONCLUSION: Oxygenation in 12 patients preoperatively, 2, 8 and 48 h after gynaecological laparotomy is described. Two patients were hypoxaemic (SaO2 <92%) 48 h postoperatively. When two different models of oxygen transport are fitted to patient data, high values of Rdiff or low values of fA2 describe the right shift in the FEO2/SaO2 curve seen in patients with oxygenation problems. These models fit patient data identically, and may be useful in quantifying postoperative hypoxaemia.

Adult↗
PubMed1999

Hypoxemia after coronary bypass surgery modeled by resistance to oxygen diffusion.

OBJECTIVE: To evaluate a model describing postoperative hypoxemia after cardiac surgery by using two variables, i.e., shunt and resistance to oxygen diffusion (Rdff). DESIGN: Estimation of these two variables in normal subjects and postoperative cardiac patients. SETTING: The pulmonary function laboratory for the normal subjects and the intensive care unit for the cardiac patients. PATIENTS/SUBJECTS: Nine postoperative cardiac patients and six healthy subjects. INTERVENTIONS: Inspired oxygen fraction was varied in normal subjects and in cardiac patients 3-6 hrs after surgery. This variation occurred in four to seven steps to achieve arterial oxygen saturations in the range 0.90-1.00. MEASUREMENTS AND MAIN RESULTS: Measurements were taken of arterial oxygen saturation, cardiac output, ventilation, and end-tidal gases at each inspired oxygen fraction. These measurements gave the following estimates for the normal subjects: shunt = 3.9+/-5.4% (mean +/- SD) and Rdiff = -5+/-16 torr/(L/min) [-0.7+/-2.2 kPa/(L/min)]; for the cardiac patients: shunt = 7.7+/-1.8% and Rdiff = 212+/-230 torr/(L/min) [28.2+/-30.6 kPa/(L/min)]. The increase in Rdiff (P = .01) was sufficient to explain the observed hypoxemia in these patients. The value for shunt was not significantly increased in the patients (p = .09). The two-variable model (shunt and Rdff) gave a better prediction of arterial oxygen saturation than a model with shunt as the only variable (p = .02). CONCLUSIONS: In cardiac patients requiring supplementary oxygen, the respiratory abnormality could, in our model, be best described by an increased Rdiff, not by an increased shunt value.

Adult↗
PubMed1999

Regulation of intracellular pH gradients by identified Na/H exchanger isoforms and a short-chain fatty acid.

Colonic luminal short-chain fatty acids (SCFA) stimulate electroneutral sodium absorption via activation of apical Na/H exchange. HT29-C1 cells were used previously to demonstrate that transepithelial SCFA gradients selectively activate polarized Na/H exchangers. Fluorometry and confocal microscopy (with BCECF and carboxy SNARF-1, respectively) are used to measure intracellular pH (pHi) in HT29-C1 cells, to find out which Na/H exchanger isoforms are expressed and if results are due to pHi gradients. Inhibition of Na/H exchange by HOE-694 identified 1) two inhibitory sites [50% inhibitory dose (ID50) = 1.6 and 0.05 microM] in suspended cells and 2) one inhibitory site each in the apical and basolateral membranes of filter-attached cells (apical ID50 = 1.4 microM, basolateral ID50 = 0.3 microM). RT-PCR detected mRNA of Na/H exchanger isoforms NHE1 and NHE2 but not of NHE3. Confocal microscopy of filter-attached cells reported HOE-694-sensitive pHi recovery in response to luminal or serosal 130 mM propionate. Confocal analysis along the apical-to-basal axis revealed that 1) luminal or serosal propionate establishes transcellular pHi gradients and 2) the predominant site of pHi acidification and pHi recovery is the apical portion of cells. Luminal propionate produced a significantly greater acidification of the apical vs. basal portion of the cell (compared with serosal propionate), but no other dependence on the orientation of the SCFA gradient was observed. Results provide direct evidence for a subcellular response that assures robust activation of apical NHE2 and dampening of basolateral NHE1 during pHi regulation.

Benzopyrans↗
PubMed1998

Reproducibility and comparability of insulin sensitivity indices measured by stable-label intravenous glucose tolerance test.

We have investigated the reproducibility of (1) insulin sensitivity (S*I) and glucose effectiveness (S*G) as measured by the stable-label (one compartment) minimal model, and (2) insulin sensitivity (S*Ib), plasma clearance rate (PCR), basal hepatic output (HGOb), and total hepatic glucose output (HGO0-240) as measured by the novel stable-label two compartment model of glucose disappearance during labelled intravenous glucose tolerance test (IVGTT) using 6,6-(2)H-glucose. Ten normal male subjects were studied on two occasions one week apart. Both models provided estimates of all indices with acceptable precision (CV of parameter estimates < or =50%). The within subject CVs of S*I and S*Ib were comparable (17% vs 19%) as were the within subject CVs of S*G and PCR (13% vs 16%). A highly significant linear relationship was observed between S*Ib and S*I (0.303 +/- 0.046 ml kg(-1) min(-1) per mU l(-1) vs 13.04 +/- 1.89 10(-4) min(-1) per mU l(-1), y = 0.0037 x + 0.0002, r = 0.90, p < 0.001; mean +/- SE), but not between PCR and S*G (1.98 +/- 0.15 ml kg(-1) min(-1) vs 0.0089 +/- 0.0005 min(-1), rs = 0.34, NS). The two compartment model provided a plausible time-profile of hepatic glucose output during IVGTT, reproducible estimates of HGOb (1.96 +/- 0.18 mg kg(-1) min(-1), 15%; mean +/- SE, within subject CV), and a highly reproducible HGO0-240 (7%; within subject CV). We conclude that the stable-label (one compartment) minimal model and the stable-label two compartment model provide reproducible estimates of parameters of glucose kinetics in normal subjects. Insulin sensitivity indices estimated by the two models are strongly linearly related.

Adult↗
PubMed1998

Effect of growth hormone treatment on postprandial protein metabolism in growth hormone-deficient adults.

Growth hormone (GH) treatment of GH-deficient adults increases lean body mass. To investigate this anabolic effect of GH, body composition and postabsorptive and postprandial protein metabolism were measured in 12 GH-deficient adults randomized to placebo or GH treatment. Protein metabolism was measured after an infusion of [1-13C]leucine before and after a standard meal at 0 and 2 mo. After 2 mo, there was an increase in lean body mass in the GH group (P < 0. 05) but no change in the placebo group. In the postabsorptive state, there was increased nonoxidative leucine disappearance (NOLD; a measure of protein synthesis) and leucine metabolic clearance rate and decreased leucine oxidation in the GH group (P < 0.05) but no change in the placebo group. After the meal, there was an increase in NOLD and oxidation in all studies (P < 0.05), but the increase in NOLD, measured as area under the curve, was greater in the GH group (P < 0.05). This study clearly demonstrates for the first time that the increase in protein synthesis in the postabsorptive state after GH treatment of GH-deficient adults is maintained in the postprandial state.

Adult↗
PubMed1996

Acid-base chemistry of the blood--a general model.

This paper describes a general model of acid-base chemistry of the blood which can be used to simulate physiological perturbation of acid-base chemistry on addition or removal of any buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acids and bases when blood is equilibrated to a new pCO2, when hydrogen ions H+ are added to the blood, or when two pools of blood with different concentrations of buffer acids and bases are mixed. The ability of the model to represent the addition or removal of any acid or base is a significant increase in functionality above the Siggaard-Andersen nomogram which is limited to simulating the effects of equilibrating the blood to a new pCO2. When used to represent the situation where blood is equilibrated at a new pCO2 the model enables calculation of the amount CO2 removed during equilibration, a further increase in functionality above the Siggaard-Andersen nomogram. In two experimental situations, equilibrating blood to a new pCO2 and addition of H+ ions, the model predictions are shown to be consistent with existing experimental data in the form of the Siggaard-Andersen nomogram.

Acid-Base Equilibrium↗
PubMed1996

Effects of intravenous infusion of lipid-free apo A-I in humans.

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.

Aged↗