Pressure-flow curves for control and hardened (diamide treated) human RBC's were obtained in capillaries of the isolated rat mesentery, in order to evaluate resistance to flow of hardened RBC's. Blood vessels were maximally dilated by an infusion of 10(-5) mol/l acetylcholine and isoprenaline and perfused with freshly collected human RBC's as well as with RBC's hardened by a treatment (hct 40%; pH 8.0; 37 degree C) with 0.5 mmol/l or 1.5 mmol/l diamide, respectively, suspended in Albumin (0.05%) - Ringer solution. The mesentery was perfused via a hydrostatic pressure reservoir. Arterio-venous pressure difference was varied from 4-10 kPa, and corresponding arteriolo-venular pressure gradients changed from about 200-500 Pa/mm. No significant difference in resistance to flow was observed between control and diamide treated cells over the whole pressure range. However, the flow through the microvascular bed was inhomogeneous upon perfusion with diamide treated cells, caused by a deceleration and stoppage of the cells at capillary narrowing (ratio of cell to vessel diameter greater than 2). The time of stagnation increased with decreasing pressure gradient.
A graded reduction of "deformability" of red blood cells (RBC's) of rats was obtained by treatment with the SH-oxidizing agent, diamide. Rigidified RBC's were injected into rats by isovolemic exchange against 60% of the native RBC's and RBC flow velocities in capillaries of rat mesentery measured. At normal mean arterial pressure RBC flow velocity decreases by 29% in rats receiving cells rigidified with 0.5 mmol . 1(-1) diamide. Surprisingly a further rigidification of erythrocytes by 1.5 mmol . 1(-1) diamide results in a decrease of flow by only 15%. During hypotension RBC flow velocities dropped precipitously to 8 +/- 15% for the 0.5 nmol . 1(-1) and to 2 +/- 6% for the 1.5 mmol . 1(-1) diamide group compared to velocities during normotension. By microscopy we observed a stop of flow in many vessels. This result outlines the importance of a normal red cell "deformability" for the maintenance of sufficient perfusion of the microcirculation, in particular at low blood pressure gradients.
Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome.
The "deformability" of rat erythrocytes can be gradually decreased by an in vitro treatment with the SH-oxidizing agent diamide. Despite of this reduced deformability the cells are retained in the circulation for many hours when reinfused into the rat. Cells rigidified with glutaraldehyde are even less deformable than diamide treated cells, but also survive for many hours. In contrast to rigidified cells of normal volumes swollen rigidified cells obtained by a heat treatment of erythrocytes are rapidly eliminated. The results support the notion that the "recognition" preceding the elimination of senescent and damaged cells of normal volumes by the reticulo-endothelial system is not solely based on their diminished deformability.
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