The Journal of clinical investigation
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The accurate definition of surface glycoprotein abnormalities in circulating platelets may provide better understanding of bleeding and thrombotic disorders. Platelet surface glycoproteins were measured on intact platelets in whole blood and platelet membrane microparticles were assayed in cell-free plasma using 125I-monoclonal antibodies. The glycoproteins (GP) studied were: GP Ib and GP IIb-IIIa, two of the major intrinsic plasma membrane glycoproteins; GMP-140, an alpha-granule membrane glycoprotein that becomes exposed on the platelet surface following secretion; and thrombospondin (TSP), an alpha-granule secreted glycoprotein that rebinds to the platelet surface. ⋯ Patients with adult respiratory distress syndrome had an increased concentration of GMP-140 and TSP on the surface of their platelets, demonstrating in vivo platelet secretion, but had no increase of platelet microparticles in their plasma. In contrast, patients after cardiac surgery with cardiopulmonary bypass demonstrated changes consistent with membrane fragmentation without secretion: a decreased platelet surface concentration of GP Ib and GP IIb with no increase of GMP-140 and TSP, and an increased plasma concentration of platelet membrane microparticles. These methods will help to define acquired abnormalities of platelet surface glycoproteins.
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The molecular mechanism of volatile anesthetic action remains unknown. Attempts to elucidate this mechanism have been complicated by the absence of models in which changes in neuronal cellular properties can be correlated with changes in whole animal anesthetic effect. In this study we describe a model where diet-induced alterations in rat brain fatty acid composition are correlated with alterations in volatile anesthetic potency. ⋯ In contrast, supplementation of the fat-deprived rats with linoleic acid (18: omega 6; 9,12-octadecadienoic acid) caused a dramatic decrease in anesthetic sensitivity, but only a small change in whole brain arachidonate content. Further analysis revealed that linoleate supplementation of fat-deprived animals resulted in a preferential normalization of the arachidonate content of brain phosphatidylinositol as compared with other brain phosphoglycerides. These results demonstrate for the first time a correlation between changes in membrane composition and anesthetic effect, and indicate that the precise fatty acid composition (perhaps in specific phospholipids) of brain is important in the mechanism of volatile anesthetic action.
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The present study evaluates the effect of acute hypercapnia on renal total CO2 (tCO2) reabsorption after inhibition of renal carbonic anhydrase. Simultaneous renal clearance studies and free-flow micropuncture studies of the superficial proximal tubule were performed on plasma-repleted Sprague-Dawley rats treated with acetazolamide, 50 mg/kg body weight. Acute hypercapnia (arterial PCO2, 120 mmHg; blood pH, 7.02) was induced by ventilation with a 10% CO2-90% O2 gas mixture. ⋯ To eliminate this effect, additional experiments were performed in which the experimental kidney was denervated before study. Denervation prevented the change in the single nephron filtration rate during acute hypercapnia, but absolute and fractional proximal tCO2 reabsorption remained elevated in comparison to denervated controls. The concentration of H2CO3 in the late proximal tubule, calculated from the measured luminal pH and bicarbonate concentration and the estimated cortical PCO2, was higher in the hypercapnic group, which was a finding compatible with H2CO3 cycling from lumen into proximal tubular cell, which provided a source of hydrogen ions for secretion.
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We have previously described a subpopulation of patients with septic shock who had a reversible depression of radionuclide-determined left ventricular ejection fraction (EF). To investigate the mechanism of this myocardial depression, an in vitro model of mammalian myocardial cell performance was established employing primary spontaneously beating rat myocardial cells. The contraction of a single cardiac cell was quantitated by recording the changes in area occupied by the cell during contraction and relaxation. ⋯ Sera from 17 critically ill nonseptic patients, from 10 patients with structural heart disease as a cause for a depressed EF, and from 12 healthy laboratory personnel, induced no significant changes in in vitro myocardial cell performance. In 20 patients during the acute phase of septic shock, the decreased EF in vivo demonstrated a significant correlation (r = +0.52, P less than 0.01) with a decrease in the extent of myocardial cell shortening in vitro. The quantitative and temporal correlation between the decreased left ventricular EF and this serum myocardial depressant substance argues for a pathophysiologic role for this depressant substance in producing the reversible cardiomyopathy seen during septic shock in humans.
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Several factors interact to maintain precise control of electrolyte transport in the mammalian cortical collecting duct. We have studied the effects of deoxycorticosterone, arginine vasopressin, and bradykinin on net transepithelial sodium and potassium transport in isolated, perfused rat cortical collecting ducts. Chronic administration of deoxycorticosterone to rats increased both sodium absorption and potassium secretion above very low basal levels. ⋯ We conclude: As in rabbits, chronic deoxycorticosterone administration to rats increases sodium absorption and potassium secretion in cortical collecting ducts perfused in vitro. Arginine vasopressin causes a reversible increase in net potassium secretion and net sodium absorption. Bradykinin in the peritubular bathing solution reversibly inhibits net sodium absorption, possibly by affecting an electroneutral sodium transport pathway.