Objective: Patients with cortisol deficiency poorly tolerate any systemic inflammatory response syndrome (SIRS), and may die if not treated with sufficient exogenous glucocorticoids. Controversy surrounds what constitutes a 'normal' adrenal response in critical illness. This study uses conventional tests for adrenal insufficiency to investigate cortisol status in patients undergoing elective coronary artery bypass surgery, a condition frequently associated with SIRS. Design: A prospective, observational study. Methods: Thirty patients with impaired left ventricular function (ejection fraction O23% !50%) underwent basal ACTH measurement, and a short cosyntropin test (250 mg, i.v.) 1 week preoperatively, and at C4 h following induction of general anaesthesia. Preoperatively, a 30 min cortisol level post cosyntropin O550 nmol/l was taken as a normal response. Results: Prior to surgery, all patients had a normal response to cosyntropin. Postoperatively, eight patients (26.7%) did not achieve stimulated cortisol levels O550 nmol/l and the mean peak cortisol postoperatively was lower (1048 vs 730 nmol/l; P!0.001). There was a significant rise in ACTH after surgery (21 vs 184 ng/l; PZ0.007) and reduction in D-cortisol post cosyntropin (579 vs 229 nmol/l; P!0.001). There was no change in basal cortisol pre-and post-operatively (447 vs 501; PZ0.4). All patients underwent routine, uneventful postoperative recovery. Conclusion: Up to one quarter of patients with a normal cortisol status preoperatively demonstrated a raised ACTH and deficient cortisol response postoperatively. Despite these responses, all patients had uneventful outcomes. These data reinforce the need for caution when interpreting results of endocrine testing following major surgery or in the intensive care environment, and that prognostic value of these results may be of limited use.
The initial separation of Na', K' and C1-ions between the aqueous phase of milk and the cytosol of the mammary secretory cell is believed tci occur within Golgi vesicles [ 11. It is predicted that after the production of lactose and the concomitant movement of water into the vesicle lumen, ions diffuse across the Golgi vesicle membrane until equilibrium is reached. There is, however, a paucity of information relating to the permeability of the Golgi vesicle membrane to small monovalent ions. Therefore we have chosen to examine Na' uptake by Golgi vesicles.Vesicles were prepared from the mammary glands of lactating rats ( 10-15 days post parturn) by a modification of the method of West [2] and were suspended in a medium containing 1 mM-NaC1, 10 mM-KCI, 300 mM-sucrose and 5 mM-Tris-Bes, pH 7.0. The activity of galactosyltransferase associated with the Golgi membranes was enriched 20-fold compared with the initial homogenate; there was only a 10% contamination with plasma membranes as judged by 5'nucleotidase activity. Na+ uptake (using ??Na as tracer) was assayed at 20°C according to the method of Gasko et a/. [3], thus intra-and extra-vesicular isotope was separated by applying aliquots of vesicles and medium to columns filled with Dowex 50 W X 8 (Tris form).Na+ uptake (at 1 mM) was found to be time dependent, reaching a point of equilibrium by 15 min. The addition of 0.1 "/o (w/v) Triton X-100 to the incubation medium abolished Na+ influx, suggesting that uptake represents real transport rather than binding of isotope to the membrane. The intravesicular volume calculated from the equilibrium uptake values was 2.64f0.20 pl/mg of protein (mean k s.E.M., n = 6). Na+ uptake was found to be temperature dependent as lowering the incubation medium temperature to 4°C reduced the initial uptake rate by 38.0f6.1% (mean f s.E.M., n = 3).Testing the effect of increasing the extravesicular Na+ concentration on Na+ influx established that uptake was saturable, the K , of uptake calculated from Hanes-Woolf plots being 2 1.4 f 2.5 mM (mean f s.E.M., tz = 4) with a V,,,,, of 29.6 f 4.6 nmol/mg of protein per 3 min ( f s.E.M., 17 = 4).To investigate the specificity of the Na' transporter we tested the effect of adding a range of monovalent cations to the incubation medium. Na+, K', Li' and choline (at 40 mM, as their CIsalts) reduced Na+ influx by 63, 49, 61 and 36"/0, respectively, indicating the order of potency of inhibition to be Na' = Lif > K' > choline. In addition, Rb' and Cs' inhibited Na+ accumulation to the same extent as K'.In order to establish if Na' uptake by Golgi vesicles occurs via a pathway sensitive to changes in membrane potential, diffusion potentials across the membrane were imposed using anions of varying passive permeability. Replacing extravesicular C1-with SCNincreased the initial rate of Na+ influx by 12%, whereas gluconate decreased it by 15%. Frusemide, amiloride and 4,4'-di-isothiocyantostilbene-2,2'-disulphonic acid (all l o -' M ) added to the incubation medium had no significant effect on the rate ...
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