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Biomedical subjects

J G Hardman

Publications and source records attributed to J G Hardman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Predicting gastric contents following trauma: an evaluation of current practice.

Trauma is often assumed to increase the risk of pulmonary aspiration of gastric contents. The 247 anaesthetists in the Trent region of England were surveyed by postal questionnaire to ascertain the current practice for identifying patients at risk of pulmonary aspiration of gastric contents following trauma. The response rate was 79%. The anaesthetists rated the reliability of several criteria when predicting 'gastric safety' and stated whether each criterion formed part of their clinical practice. Interval of eating to injury was the most used (88%) and highest rated criterion (4/5) followed by use of opioids. Presence or absence of bowel sounds was the least used (7%) and lowest rated criterion (0/5). Currently there is little evidence that the commonly used criteria accurately identify 'at-risk' patients. There is little evidence that trauma increases the risk of aspiration although a number of factors associated with trauma are known to delay gastric emptying.

Anesthesia↗
PubMed1999

Estimating venous admixture using a physiological simulator.

Estimation of venous admixture in patients with impaired gas exchange allows monitoring of disease progression, efficacy of interventions and assessment of the optimal inspired oxygen fraction. A pulmonary artery catheter allows accurate measurement, although the associated risks preclude its use solely for estimation of venous admixture. Non-invasive methods require assumed values for physiological variables. Many of the required data (e.g. haemoglobin concentration (Hb), base excess, inspired oxygen fraction, arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, temperature) are available routinely in the intensive therapy unit. We have compared a typical iso-shunt-style estimation of venous admixture (assuming Hb, base excess, PaCO2 and temperature), and estimation using the Nottingham physiology simulator (NPS), with measured data. When the arteriovenous oxygen content difference (CaO2-CvO2) was assumed to be 50 ml litre-1, the 95% limits of agreement (LA95%) for venous admixture using the NPS were -3.9 +/- 8.5% and using an iso-shunt-style calculation, -6.4 +/- 10.6%. CaO2-CvO2 was 41.1 ml litre-1 in the patients studied, consistent with previous studies in the critically ill. When CaO2-CvO2 was assumed to be 40 ml litre-1, LA95% values were 0.5 +/- 8.2% and -2.1 +/- 10.1%, respectively.

Carbon Dioxide↗
PubMed1999

Estimation of alveolar deadspace fraction using arterial and end-tidal CO2: a factor analysis using a physiological simulation.

The alveolar deadspace as a fraction of alveolar ventilation (VDalv/VTalv), while technically difficult to measure, is an objective monitor of pulmonary disease progression and a predictor of successful weaning from mechanical ventilation. The aim of the study was to examine the relationship between the arterial to end-tidal PCO2 gradient (Pa-E'CO2) and VDalv/VTalv and between (Pa-E'CO2)/PaCO2 and VDalv/VTalv using the Nottingham Physiology Simulator, an original, validated physiology simulation. The relationships were observed while pulmonary shunt, anatomical deadspace, ventilatory minute volume and metabolic rate were varied. The relationship between Pa-E'CO2 and VDalv/VTalv was non-linear and was affected significantly by all the factors except anatomical deadspace. The relationship between (Pa-E'CO2)/PaCO2 and VDalv/VTalv (best fit: VDalv VTalv = 1.135 x (Pa-E'CO2)/PaCO2-0.005) during normal physiological conditions was approximately linear and less influenced by physiological variation. Shunt and anatomical deadspace caused some inaccuracy, although they are unlikely to prevent the clinical usefulness of this formula.

Carbon Dioxide↗
PubMed1999

The influence of breathing system filters on paediatric capnography.

Breathing system filters are in common use during paediatric anaesthesia. Expired gas sampling from the patient side of these filters may contaminate and saturate the sampling line, while sampling from the machine side may cause underestimation of end-tidal carbon dioxide (PECO 2). The aim of this investigation was to elucidate the degree of underestimation of PECO 2 induced by sampling from the machine side of a breathing system filter. Ten spontaneously breathing children and ten children receiving mechanical ventilation under general anaesthesia were studied. PECO 2 was higher at the patient side of the filter in both ventilated and spontaneously breathing groups (P<0.002 for each). The bias in measuring at the machine side of the filter was significantly greater in the spontaneously breathing children as compared with the mechanically ventilated children (-1.8 vs -0.7 kPa; P<0.004).

Anesthesia, General↗
PubMed1998

A physiology simulator: validation of its respiratory components and its ability to predict the patient's response to changes in mechanical ventilation.

We aimed to validate the mathematical validity and accuracy of the respiratory components of the Nottingham Physiology Simulator (NPS), a computer simulation of physiological models. Subsequently, we aimed to assess the accuracy of the NPS in predicting the effects of a change in mechanical ventilation on patient arterial blood-gas tensions. The NPS was supplied with the following measured or calculated values from patients receiving intensive therapy: pulmonary shunt and physiological deadspace fractions, oxygen consumption, respiratory quotient, cardiac output, inspired oxygen fraction, expired minute volume, haemoglobin concentration, temperature and arterial base excess. Values calculated by the NPS for arterial oxygen tension and saturation (PaO2 and SaO2), mixed venous oxygen tension and saturation (PvO2 and SvO2), arterial and mixed venous carbon dioxide tension (PaCO2 and PvCO2) and arterial pH were accurate compared with measured values. Subsequently, arterial gas responses to changes in minute volume of FiO2 were measured in 31 patients and were compared with the NPS prediction for each response. The 95% limits of agreement in predicting the magnitude of change were: arterial oxygen tension -2.07 to 2.47 kPa; PaCO2 -0.33 to 0.67 kPa; and pH -0.023 to 0.033. This investigation has validated respiratory components of the NPS. We recommend the NPS as a clinical tool for predicting the effects of alterations in mechanical ventilation in stable patients in the intensive care unit.

Adult↗
PubMed1997

End-tidal carbon dioxide measurement and breathing system filters.

Breathing system filters are recommended for use during general anaesthesia. Manufacturers of gas sampling equipment recommend that gas is sampled from the 'machine side' of these filters, thereby avoiding contamination of the sampling line and waterlogging in the case of heat and moisture exchangers. The aim of this study was to investigate differences between the measured end-tidal carbon dioxide values at either side of the filter. Fifteen adults were studied during mechanical ventilation and 15 during spontaneous ventilation under general anaesthesia. End-tidal carbon dioxide values were significantly lower at the machine side of the filter in both groups (p = 0.00001). The measurement error induced by the inclusion of the breathing system filter was significantly greater in the spontaneously breathing group (p = 0.0004).

Adult↗
PubMed1986

Activation of soluble guanylate cyclase by arachidonic acid and 15-lipoxygenase products.

The activity of soluble guanylate cyclase can be increased by exposure of the enzyme to arachidonic acid or to some oxidized metabolites of the fatty acid. We have tried to determine whether activation of the enzyme by arachidonate requires that the fatty acid be converted to an oxidized metabolite, either by a possible trace contaminant of a lipoxygenase or by guanylate cyclase itself, which contains a heme moiety. Soluble guanylate cyclase purified from bovine lung was activated 4-6-fold by arachidonic acid. This activation was not dependent on the presence of oxygen in the incubation medium. No detectable metabolites of arachidonic acid were formed during incubation with soluble guanylate cyclase. Addition of soybean lipoxygenase to the incubation did not increase activation by arachidonic acid. The inhibitors of lipoxygenase activity, nordihydroguaiaretic acid and eicosatetraynoic acid, had direct effects on soluble guanylate cyclase and interfered with its activation by arachidonate, whereas another lipoxygenase inhibitor, BW 755 C, did not. The data suggest that arachidonic acid increases the activity of guanylate cyclase by direct interaction with the enzyme rather than by being converted to an active metabolite.

Animals↗
PubMed1985

Differences in the association of calmodulin with cyclic nucleotide phosphodiesterase in relaxed and contracted arterial strips.

Changes in the concentration of cytosolic Ca2+ are assumed to alter the activity of Ca2+-calmodulin-sensitive cyclic nucleotide phosphodiesterase in intact cells. However, this assumption is based on indirect evidence and by analogy from studies of enzyme activities in broken cell systems. We have developed a procedure for estimating the fraction of Ca2+-calmodulin-sensitive phosphodiesterase that is in an activated, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) sensitive state in intact porcine coronary artery strips. The experimental approach involves homogenization of the strips and assay of cyclic guanosine monophosphate (cyclic GMP) phosphodiesterase activity under conditions that retard changes in the amount of the complex Ca2+-calmodulin-phosphodiesterase. Our findings indicate that cyclic GMP phosphodiesterase in intact coronary artery strips does associate with Ca2+-calmodulin and that interventions that change the concentration of Ca2+ in the cytosol of the intact strip change the extent of this functional association. Exposure to histamine (10 or 100 microM) or 50 mM KCl caused contraction and an increase in EGTA-sensitive cyclic GMP phosphodiesterase activity. Isoproterenol-induced relaxation of tissues that had been caused to contract with 10 microM histamine was accompanied by a reduction in EGTA-sensitive cyclic GMP phosphodiesterase activity to the same level as that present before contraction was initiated.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1984

Cyclic nucleotides and regulation of vascular smooth muscle.

Cyclic AMP probably plays an important role in blood-vessel relaxation caused by beta-adrenergic agonists and other agents, including inhibitors of cyclic nucleotide phosphodiesterases. Cyclic GMP may participate in blood-vessel relaxation caused by drugs such as nitroglycerin and nitroprusside and by agents that require the endothelium for their relaxing effects. The significance of elevated levels of cyclic GMP in response to contraction-producing agents is unknown. Cyclic nucleotides may modulate vascular smooth-muscle contraction by regulating the phosphorylation of multiple proteins involved in the action and distribution of calcium. The relative importance of different potential sites of regulation by cyclic nucleotides may vary among different blood vessels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Calcium-induced release from platelet membranes of fatty acids that modulate soluble guanylate cyclase.

Incubation of rat or rabbit platelet membranes with Ca++ induced the release of modulators of soluble guanylate cyclase. These modulators increased basal activity and inhibited sodium nitroprusside-stimulated activity in the absence or presence of dithiothreitol. The release, but not the effects, of the modulators was inhibited by trifluoperazine and by mepacrine. Indomethacin and oxyphenbutazone did not influence the release or effects of the modulators. The factors were identified as arachidonic and linoleic acids. These fatty acids produced comparable effects on crude soluble guanylate cyclase from platelets and on the homogeneously purified enzyme from bovine lung. In the presence of MgCl2, the maximal increase in basal activity was observed at 10 to 30 microM arachidonic or linoleic acid with the crude enzyme and at 3 to 6 microM with the purified enzyme. Inhibition of basal activity was observed at higher concentrations. Half-maximal inhibition of Mg++-supported, sodium nitroprusside-augmented activity was observed at 3 to 10 microM fatty acid. The effects of arachidonic acid occurred without a lag period and were quickly reversible. These data demonstrate that unsaturated fatty acids can be released from platelet membranes by a Ca++-dependent process in amounts that are high enough to alter soluble guanylate cyclase activity. The data also indicate that unsaturated fatty acids exert their effects on soluble guanylate cyclase without having to be converted to peroxides by other enzymes.

Animals↗
PubMed1980

Cyclic nucleotide phosphodiesterase activities from pig coronary arteries. Lack of interconvertibility of major forms.

DEAE-cellulose chromatography, with or without dithiothreitol and over a pH range of 6.0 to 8.5, resolved two phosphodiesterase activities (peaks I and II) from the soluble fraction of pig coronary arteries. The activity of peak I was increased by calmodulin (3-7-fold), whereas that of peak II was not. Chromatography of peak I on Biol-Gel A-0.5 m columns resolved two peaks of phosphodiesterase activity (peaks Ia and Ib). Peak Ia was eluted in the presence or absence of 0.1 M KCl and was relatively insensitive to calmodulin. Peak Ib was eluted only in the presence of KCl and was sensitive to calmodulin. The substrate specificity and kinetic behavior were the same for peaks I, Ia, and Ib. Repeated gel chromatography of either peak Ia or Ib, under appropriate conditions, yielded a mixture of peaks Ia and Ib. Peak Ia appears to be a reversible aggregate of peak Ib. Gel chromatography of peak II resolved only one phosphodiesterase activity, which was eluted without KCl, was highly specific for cyclic AMP, was not sensitive to calmodulin and migrated differently on the gel column than either peak Ia or Ib. Sucrose density gradient centrifugation of the soluble fraction from pig coronary arteries in the presence or absence of dithiothreitol resolved two peaks of phosphodiesterase activity (6.6 S and 3.6 S) which were similar to peaks I and II separated by DEAE-cellulose chromatography with regard to their substrate specificity and their sensitivity to calmodulin. Upon recentrifugation, each of the two peaks of phosphodiesterase activity gave a single peak of activity which migrated with the same S value as did its parent. These results indicate that the two major forms of phosphodiesterase of pig coronary arteries, which are representative of those found in many tissues, are not interconvertible in cell-free systems.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

The calcium accumulation in a microsomal fraction from porcine coronary artery smooth muscle. A study of the heterogeneity of the fraction.

1. Microsomes prepared from the combined media and intima of pig coronary artery, take up Ca in an ATP-dependent way. This uptake is stimulated by oxalate. 2. Conditions have been determined to optimize the preparation of the microsomes in terms of their Ca accumulation activity. Careful homogenization of the tissue mince in 0.25 M sucrose by means of a Potter-Elvehjem homogenizer gives microsomal preparations with the highest specific activity for Ca accumulation. 3. Arguments are presented to support the hypothesis that, even in the absence of oxalate, Ca accumulation occurs into the lumen of the vesicles, and that these vesicles have a low Ca permeability. 4. Density gradient analysis shows that the microsomal fraction prepared from pig coronary artery media and intima is composed of vesicles that are heterogeneous in enzymatic composition. 5. Adenylate cyclase appears to be a predominantly plasma membrane-bound enzyme. Rotenone-insensitive NADH-cytochrome c reductase and choline phosphotransferase, two putative markers for internal membranes, give distinct banding patterns on on isopycnic centrifugation, indicating different intracellular localization. 6. There is a difference between the density gradient distribution pattern of Ca uptake measured in the presence or absence of oxalate. The latter coincides more closely with plasma membrane markers. The former resembles more the distribution of rotenone-insensitive NADH-cytochrome c reductase.

Animals↗
PubMed1978

The effect of adrenocorticotropin and nucleotides on Ca2+ uptake in adrenal cortical microsomal vesicles.

Rat and bovine adrenal cortical microsomal fractions isolated at 27,000 x g and 105,000 x g accumulated Ca2+ by a nonmitochondrial, ATP-dependent uptake system that was stimulated by ammonium oxalate. ACTH (2 mU/ml) significantly increased Ca2+ uptake in bovine adrenal cortical microsomes and in adrenal microsomes from acutely hypophysectomized rats, but only when the hormone was preincubated with intact tissue and not when it was added after homogenization. ACTH did not stimulate C2+ uptake in adrenal microsomes isolated from nonhypophysectomized, ether-stressed rats, in which basal Ca2+ uptake was higher than that observed in microsomes from hypophysectomized animals. The peptides oxytocin, insulin, and TSH did not stimulate Ca2+ uptake by adrenal cortical microsomes. ACTH preincubated with intact tissue had no effect on Ca2+ uptake in microsomes from liver, kidney, esophagus, or aorta. cAMP, 5'-AMP, and several other nucleotides, nucleosides, and related compounds stimulated adrenal cortical microsomal Ca2+ uptake by as much as 540% of control. The stimulatory effects of nucleotides, unlike those of ACTH, were apparent even when the agents were added after homogenization. However, like ACTH, the nucleotides were unable to stimulate Ca2+ uptake when they were added to isolated membrane vesicles during Ca2+ uptake measurements. It is suggested that the microsomal Ca2+ uptake system may respond to physiological stimulants and regulate Ca2+ availability in the intact cell.

Adrenal Cortex↗