Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. Results One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0–3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. Conclusion Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

To characterize different transport compartments in the urinary bladder epithelium of postabsorptive turtles, the electrolyte composition of individual cells was determined using electron microprobe analysis. After blocking the transepithelial Na transport, the short-circuit current decreased from positive to negative values (from 26.5 +/- 17.7 to -3.9 +/- 2.9 after ouabain and from 25.4 +/- 17.2 to -8.0 +/- 5.1 microA/cm2 after amiloride). Whereas under control conditions the Na and K concentrations were similar in all cell types and the same was true for Cl in most of the cells, some cells exhibited very low Cl concentrations. The epithelial cells were subdivided according to their electrolyte composition into ouabain-sensitive and ouabain-insensitive ones. In the ouabain-sensitive cells, which made up the majority of epithelial cells and showed a relatively high Cl concentration (about 36 mmol/kg wet weight), the Na concentration increased after ouabain by about 90 mmol/kg wet weight and the K concentration decreased by a similar amount. Since these alterations could largely be prevented when amiloride was applied before ouabain, it is suggested that the granular and basal cells form a syncytial Na transport compartment similar to that in other multilayered epithelia. The ouabain-insensitive cells, in which almost no alteration in Na and K concentrations was observed after ouabain, were subdivided into a Cl-rich (34.6 +/- 7.6 mmol/kg wet weight) and a Cl-poor (12.0 +/- 5.6 mmol/kg wet weight) population. Since in these cells no large mucin granules were detectable, they are regarded as carbonic anhydrase-rich cells involved in H and HCO3 transport.

Electron microprobe analysis was used to determine cellular electrolyte concentrations in rabbit urinary bladder. Under control conditions the mean cellular electrolyte concentrations were for Na 11.6 +/- 2.0, for K 124.1 +/- 15.3, and for Cl 26.0 +/- 5.1 mmol/kg wet weight. The dry weight content was 19.0 +/- 2.0 g/100 g. Inhibition of the Na/K-pump with ouabain resulted in drastic changes of the cellular element concentrations. Similar changes also occurred when in addition to ouabain the apical side was kept Na-free. In all epithelial layers the Na and Cl concentrations increased by 90 and 30 mmol/kg wet weight, whereas the K concentration and the dry weight content decreased by 90 mmol/kg wet weight and 6 g/100 g wet weight, respectively. With Na-free choline-Ringer's solution on the basal side ouabain led to a decrease in the K concentration by about 60 mmol/kg wet weight while the Na and Cl concentrations remained unchanged. These data indicate that the basolateral membrane is permeable to Na, choline, Cl, and K. Nystatin produced drastic changes in the cellular electrolyte concentrations when Na- or Rb-sulfate Ringer's solutions were present on the apical side. With Na-sulfate Ringer's solution the Na concentration increased by about 25, the Cl concentration by 30 mmol/kg wet weight and the dry weight content decreased by 4.5 g/100 g, respectively. With Rb-Ringer's solution about 20 mmol/kg wet weight of the cellular K was exchanged against Rb. The concentration changes were identical in all epithelial layers supporting the idea that the rabbit urinary bladder represents a functional syncytium with regard to the transepithelial Na transport.