Hemoglobin vesicles reduce hypoxia-related inflammation in critically ischemic hamster flap tissue

OBJECTIVES: The aim of this study was to investigate the effect of a highly viscous, left-shifted hemoglobin vesicle solution (HbV) on the hypoxia-related inflammation and the microcirculation in critically ischemic peripheral tissue. DESIGN: Randomized prospective study. SETTING: University laboratory. SUBJECTS: Twenty-four male golden Syrian hamsters. INTERVENTIONS: Island flaps were dissected from the back skin of anesthetized hamsters for assessment with intravital microscopy. The flap included a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. One hour after completion of the preparation, the animals received an injection of 25% of total blood volume of 0.9% NaCl or NaCl suspended with HbVs at a concentration of 5 g/dL (HbV5) or 10 g/dL (HbV10). MEASUREMENTS AND MAIN RESULTS: Plasma viscosity was increased from 1.32 cP to 1.61 cP and 2.14 cP after the administration of HbV5 and HbV10, respectively (both p < .01). Both HbV solutions raised partial oxygen tension (Clark-type microprobes) in the ischemic tissue from approximately 10 torr to 17 torr (p < .01), which was paralleled by an increase in capillary perfusion by > 200% (p < .01). The 50% increase in macromolecular capillary leakage found over time in the control animals was completely abolished by the HbV solutions (p < .01), which was accompanied by a > 50% (p < .01) reduction in cells immunohistochemically stained for tumor necrosis factor-alpha and interleukin-6 and in leukocyte counts, whereas no such changes were observed in the anatomically perfused, normoxic tissue. CONCLUSIONS: Our study suggests that in critically ischemic, hypoxic peripheral tissue, hypoxia-related inflammation may be reduced by a top-load infusion of HbV solutions. We attributed this effect to a restoration of tissue oxygenation and an increase in plasma viscosity, both of which may have resulted in attenuation of secondary microcirculatory impairments.

Gentle Giant - Fierce Fighter: People Power from the League to the Legislature – Dorothy Eck “In the Crucible of Change”

Abstract to be posted.

Time-dependent interactions of the two porphyrinic compounds chlorin e6 and mono-L-aspartyl-chlorin e6 with phospholipid vesicles probed by NMR spectroscopy

The distribution processes of chlorin e6 (CE) and monoaspartyl-chlorin e6 (MACE) between the outer and inner phospholipid monolayers of 1,2-dioleoyl-phosphatidylcholine (DOPC) vesicles were monitored by 1H NMR spectroscopy through analysis of chemical shifts and line widths of the DOPC vesicle resonances. Chlorin adsorption to the outer vesicle monolayer induced changes in the DOPC 1H NMR spectrum. Most pronounced was a split of the N-methyl choline resonance, allowing for separate analysis of inner and outer vesicle layers. Transbilayer distribution of the chlorin compounds was indicated by time-dependent characteristic spectral changes of the DOPC resonances. Kinetic parameters for the flip-flop processes, that is, half-lives and rate constants, were obtained from the experimental data points. In comparison to CE, MACE transbilayer movement was significantly reduced, with MACE remaining more or less attached to the outer membrane layer. The distribution coefficients for CE and MACE between the vesicular and aqueous phase were determined. Both CE and MACE exhibited a high affinity for the vesicular phase. For CE, a positive correlation was found between transfer rate and increasing molar ratio CE/DOPC. Enhanced membrane rigidity induced by increasing amounts of cholesterol into the model membrane was accompanied by a decrease of CE flip-flop rates across the membrane. The present study shows that the movement of porphyrins across membranes can efficiently be investigated by 1H NMR spectroscopy and that small changes in porphyrin structure can have large effects on membrane kinetics.

FDG uptake in giant cell tumor of the tendon sheath in a patient restaged for gastrointestinal stroma tumor (GIST)

A 70-year-old man known for recurrent abdominal gastrointestinal stroma tumor presented with a suspicious peritoneal mass demonstrated by an abdominal CT scan. Whole-body PET showed focal FDG uptake in the right hip, whereas the peritoneal mass was FDG negative. Histologic work-up of the PET positive lesion surprisingly revealed a giant cell tumor of the tendon sheath. The benignity of the peritoneal mass was confirmed by its disappearance in repeated CT scans. In general, focally increased FDG uptake should be subject to further investigations, especially in localizations that are not consistent with typical metastatic pathways of the former primary tumor.

Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice

Local hypoxia, as due to trauma, surgery, or arterial occlusive disease, may severely jeopardize the survival of the affected tissue and its wound-healing capacity. Initially developed to replace blood transfusions, artificial oxygen carriers have emerged as oxygen therapeutics in such conditions. The aim of this study was to target primary wound healing and survival in critically ischemic skin by the systemic application of left-shifted liposomal hemoglobin vesicles (HbVs). This was tested in bilateral, cranially based dorsal skin flaps in mice treated with a HbV solution with an oxygen affinity that was increased to a P(50) (partial oxygen tension at which the hemoglobin becomes 50% saturated with oxygen) of 9 mmHg. Twenty percent of the total blood volume of the HbV solution was injected immediately and 24 h after surgery. On the first postoperative day, oxygen saturation in the critically ischemic middle flap portions was increased from 23% (untreated control) to 39% in the HbV-treated animals (P < 0.05). Six days postoperatively, flap tissue survival was increased from 33% (control) to 57% (P < 0.01) and primary healing of the ischemic wound margins from 6.6 to 12.7 mm (P < 0.05) after HbV injection. In addition, higher capillary counts and endothelial nitric oxide synthase expression (both P < 0.01) were found in the immunostained flap tissue. We conclude that left-shifted HbVs may ameliorate the survival and primary wound healing in critically ischemic skin, possibly mediated by endothelial nitric oxide synthase-induced neovascularization.