Use of Intramuscular Ephedrine Sulfate During Kidney Transplantation.

Hypotension during kidney transplantation can be common. Vasopressor use during these procedures is often avoided, with a fear of decreasing renal perfusion in the transplanted kidney. However, adequate perfusion for the rest of the body is also necessary, and given that these patients often have underlying hypertension or other comorbid conditions, an appropriate mean arterial pressure (MAP) has to be maintained. Intramuscular injections of ephedrine have been studied in the anesthesiology literature in a variety of case types, and it is seen as a safe and effective method to boost MAP. We present a case series of three patients who underwent renal transplantation and who received an intramuscular injection of ephedrine for hypotension control. The medication worked well for increasing blood pressures without apparent side effects. All three patients were followed for more than one year, and all patients had good graft function at the end of that time period. This series shows that while further research is necessary in this arena, intramuscular ephedrine may have a place in the management of persistent hypotension in the operating room during kidney transplantation.

Decreased Cerebral Perfusion Under Anesthesia During Radiation Treatment: A Case Report.

Radiation therapy allows patients to receive focused radiation to a tumor. Some patients require anesthesia for their daily treatments. For head and neck tumors, a thermoplastic mask is created to minimize movement. We describe a case where a patient's neck circumference increased during the course of treatment. Given that the patient was under anesthesia for each treatment, he was not able to relay the tightness of the mask. This led to cerebral hypoxia. Cerebral oximetry confirmed this diagnosis, and the patient's mask was refitted-remaining anesthetics were uneventful. Mask fitness should be reassessed during the treatment series.

Nasopharyngeal Airway Causing Partial Tracheal Obstruction During an Awake Nasotracheal Fiberoptic Intubation: A Case Report.

Awake nasotracheal fiberoptic intubations are used to manage difficult airways. Nasopharyngeal airways can be placed into the nostril to facilitate fiberoptic intubation and has been shown to be a useful pathfinder. We describe a case where this nasopharyngeal airway was inadvertently advanced with the bronchoscope and led to partial tracheal obstruction. To our knowledge, this represents the first reported case of this mishap. Aspiration of the nasopharyngeal airway can lead to complete airway obstruction and devastating consequences. Simple techniques such as attaching a hemostat or using an assistant to hold on to the nasopharyngeal airway may prevent this occurrence.

Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.

PURPOSE: Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv(-/-) mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv(-/-) retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. METHODS: Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv(-/-) mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv(-/-) pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. RESULTS: Expression of GPR91 was higher in Hjv(-/-) retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv(-/-) retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv(-/-) retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. CONCLUSIONS: G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization.

Iron-mediated retinal degeneration in haemojuvelin-knockout mice.

Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE (human leucocyte antigen-like protein involved in iron homoeostasis), transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Recent studies have established the expression of all of the five genes in the retina, indicating their importance in retinal iron homoeostasis. Previously, we demonstrated that HJV is expressed in RPE (retinal pigment epithelium), the outer and inner nuclear layers and the ganglion cell layer. In the present paper, we report on the consequences of Hjv deletion on the retina in mice. Hjv-/- mice at ≥18 months of age had increased iron accumulation in the retina with marked morphological damage compared with age-matched controls; these changes were not found in younger mice. The retinal phenotype in Hjv-/- mice included hyperplasia of RPE. We isolated RPE cells from wild-type and Hjv-/- mice and examined their growth patterns. Hjv-/- RPE cells were less senescent and exhibited a hyperproliferative phenotype. Hjv-/- RPE cells also showed up-regulation of Slc7a11 (solute carrier family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger). BMP6 (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv-/- RPE cells, confirming that retinal cells require HJV for induction of hepcidin via BMP6 signalling. HJV is a glycosylphosphatidylinositol-anchored protein, and the membrane-associated HJV is necessary for BMP6-mediated activation of hepcidin promoter in RPE cells. Taken together, these results confirm the biological importance of HJV in the regulation of iron homoeostasis in the retina and in RPE.